3.4.24.69: bontoxilysin
This is an abbreviated version!
For detailed information about bontoxilysin, go to the full flat file.
Word Map on EC 3.4.24.69
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3.4.24.69
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pain
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nerve
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spastic
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dystonias
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bonts
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facial
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palsy
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bladder
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overact
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limb
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botulism
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paralysis
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neuromuscular
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spasm
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placebo
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double-blinded
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headache
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detrusor
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migraine
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incontinence
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cosmetic
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relief
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rehabilitation
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placebo-controlled
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neurogenic
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sphincter
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satisfaction
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aesthetic
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dysphagia
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snap-25
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ptosis
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involuntary
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anticholinergic
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eyelid
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strabismus
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intravesical
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wrinkle
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urodynamic
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electromyography
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flexor
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masseter
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voice
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rectus
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fissure
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filler
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adductor
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antitoxin
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physiotherapy
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pneumatic
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baclofen
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molecular biology
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medicine
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drug development
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analysis
- 3.4.24.69
- pain
- nerve
- spastic
- dystonias
-
bonts
-
facial
- palsy
- bladder
-
overact
- limb
- botulism
- paralysis
- neuromuscular
- spasm
-
placebo
-
double-blinded
- headache
- detrusor
- migraine
- incontinence
-
cosmetic
-
relief
-
rehabilitation
-
placebo-controlled
-
neurogenic
-
sphincter
-
satisfaction
-
aesthetic
- dysphagia
- snap-25
- ptosis
-
involuntary
-
anticholinergic
- eyelid
- strabismus
-
intravesical
-
wrinkle
-
urodynamic
-
electromyography
- flexor
- masseter
- voice
-
rectus
- fissure
-
filler
- adductor
- antitoxin
-
physiotherapy
-
pneumatic
- baclofen
- molecular biology
- medicine
- drug development
- analysis
Reaction
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates =
Synonyms
abobotulinumtoxinA, antigen E, Balc424, BoNT, BoNT A, BoNT B, BoNT E, BoNT F, BoNT F/A, BoNT LC, BoNT LC/A, BoNT serotype A, BoNT serotype E, BoNT serotype F, BoNT-A, BoNT-C, BoNT-D, BoNT-E, BoNT-F, BoNT/A, BoNT/A LC, BoNT/A Lc endopeptidase, BoNT/A-LC, BoNT/A1, BoNT/A2, BoNT/A3, BoNT/A4, BoNT/A5, BoNT/A6, BoNT/A8, BoNT/B, BoNT/B light chain protease, BoNT/B-LC, BoNT/B1, BoNT/B6, BoNT/C, BoNT/C1, BoNT/C1-LC, BoNT/C3, BoNT/CD, BoNT/D, BoNT/E, BoNT/F, BoNT/F proteolytic F toxin, BoNT/F-LC, BoNT/F1, BoNT/F5, BoNT/F6, BoNT/F7, BoNT/F9, BoNT/FA, BoNT/G, BoNT/HA, BoNT/T, BoNT/X, BoNTA, BoNTA endopeptidase, BoNTB, BoNTC, BoNTE, BoNTF, Bontoxilysin C1, botox A, botulinum A neurotoxin light chain, Botulinum neurotoxin, botulinum neurotoxin a, botulinum neurotoxin A light chain, botulinum neurotoxin A protease, botulinum neurotoxin A subtype 1, botulinum neurotoxin A subtype 2, botulinum neurotoxin A subtype 6, botulinum neurotoxin A3, botulinum neurotoxin A4, botulinum neurotoxin A8 subtype, botulinum neurotoxin B, botulinum neurotoxin B protease, botulinum neurotoxin C, botulinum neurotoxin D light chain, botulinum neurotoxin E, botulinum neurotoxin endopeptidase, botulinum neurotoxin F, botulinum neurotoxin serotype A, botulinum neurotoxin serotype A endopeptidase, botulinum neurotoxin serotype A light chain, botulinum neurotoxin serotype A protease, botulinum neurotoxin serotype B, botulinum neurotoxin serotype BA, botulinum neurotoxin serotype C1, botulinum neurotoxin serotype C1 light chain protease, botulinum neurotoxin serotype D, botulinum neurotoxin serotype E, botulinum neurotoxin serotype F, botulinum neurotoxin serotype FA, botulinum neurotoxin serotype G, botulinum neurotoxin serotype H, botulinum neurotoxin subtype A, botulinum neurotoxin subtype A3, botulinum neurotoxin subtype A4, botulinum neurotoxin subtype B6, botulinum neurotoxin subtype F5, botulinum neurotoxin type A, botulinum neurotoxin type A light chain, botulinum neurotoxin type B, botulinum neurotoxin type C, botulinum neurotoxin type D, botulinum neurotoxin type E, botulinum neurotoxin type F, botulinum neurotoxin type F light chain, botulinum neurotoxin type G, botulinum neurotoxin type HA, botulinum neurotoxin X, Botulinum neurotoxin-A, botulinum toxin, botulinum toxin C3, botulinum toxin serotype E, botulinum toxin serotype F, botulinum toxin type A, botulinum toxin type B, botulinum toxin type F, Botulinumtoxin A, BoTxA, C2 toxin, CDC69016, Clostridium botulinum A2 neurotoxin, Clostridium botulinum C2 toxin, Clostridium botulinum neurotoxin, Clostridium botulinum neurotoxin A1, Clostridium botulinum neurotoxin F, Clostridium botulinum neurotoxin serotype A, Clostridium botulinum neurotoxin serotype A light chain, Clostridium botulinum neurotoxin type E, Clostridium botulinum serotype D neurotoxin, CNT endopeptidase, D-4947 L-TC, daxibotulinumtoxinA, HCB, HCE, incobotulinumtoxinA, LC/A, LC/D, LC/F5, LC/HA, LC/X, LCA, LcB, lcc1, LCD, LCE, LCF, LHn/D, More, mosaic toxin, neurotoxin A, NT, onabotulinumtoxinA, serotype D botulinum neurotoxin, subtype A4 neurotoxin, TeNT, Tetanus neurotoxin, type A BoNT, type A botulinum neurotoxin, type A botulinum neurotoxin light chain, type A botulinum neurotoxin protease, type F toxin
ECTree
3.4.24.69 bontoxilysinAdvanced search results
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results (Substrates Products
Substrates Products on EC 3.4.24.69 - bontoxilysin
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SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5-carboxyfluorescein-TRIDEANQRATK-Dabcyl-6-aminohexanoic acid-CONH2 + H2O
?
-
-
-
-
?
5-carboxyfluorescein-TRIDEANQRATK-Dabcyl-norleucine-CONH2 + H2O
?
-
-
-
-
?
7-hydroxy-4-methylcoumarin-3-acetyl-TRIDEANQRATK-Dabcyl-6-aminohexanoic acid-CONH2 + H2O
?
-
-
-
-
?
7-hydroxy-4-methylcoumarin-3-acetyl-TRIDEANQRATK-Dabcyl-CONH2 + H2O
?
-
-
-
-
?
7-hydroxy-4-methylcoumarin-3-acetyl-TRIDEANQRATK-Dabcyl-norleucine-CONH2 + H2O
?
-
-
-
-
?
Ac-ERDQKLSELDDRADALQAG-(7-methoxy-4-methylcoumaryl)Lys-SQ-diaminopropionic acid(2,4-dinitrophenyl)-ESSAAKLKRKYWWKNLK-NH2 + H2O
?
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development of a FRET peptide substrate, based on the native substrate binding site of human VAMP2 residues 55-94, and evaluation for enzymatic cleavage by the BoNT/B light chain protease, overview. For the synthesis position 74 is mutated to Lys in order to couple 7-methoxycoumarin-4-acetic acid, MCA, to the amine via an amide bond, in part to aid in the flexibility of the MCA to allow free rotation away from the active site and not affect binding and/or cleavage of the peptide. At position 77 the native Phe is replaced with the unnatural amino acid diaminopropionic acid to facilitate coupling of 2,4-dinitrophenyl to the peptide. Thr79 is mutated to a serine increasing kcat 2fold without affecting Km
-
-
?
Ac-IIGNLRH(Nle)ALD(Nle)GNEIDTQNRQIDRI(Nle)EKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2 + H2O
Ac-IIGNLRH(Nle)ALD(Nle)GNEIDTQNRQIDRI(Nle)EKADSNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)L-NH2
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i.e. peptide PL51, a SNAP-25-NH2in which all methionines were replaced by nonoxidizable Nle
-
-
?
Ac-IIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2 + H2O
Ac-IIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)L-NH2
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i.e. peptide PL50, a SNAP-25-NH2 acetylated at positions 156 to 203 [(pNO2-Phe)197, (1-pyrenylalanine)200, Nle202]
-
-
?
Ac-KSDSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)LGSG-NH2 + H2O
Ac-KSDSNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)LGSG-NH2
-
-
-
-
?
Ac-SNKTIDEANQRATKML-NH2 + H2O
Ac-SNKTIDEANQ + RATKML-NH2
-
synaptosomal protein
-
?
Ac-SNKTRIDCANQRATKML-NH2 + H2O
Ac-SNKTRIDCANQ + RATKML-NH2
-
-
-
?
Ac-SNKTRIDEAN(1-pyrenylalanine)RA(pNO2-Phe)K(Nle)L-NH2 + H2O
Ac-SNKTRIDEAN(1-pyrenylalanine) + RA(pNO2-Phe)K(Nle)L-NH2
-
-
-
-
?
Ac-SNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2 + H2O
Ac-SNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)L-NH2
-
-
-
-
?
Ac-SNKTRIDEANQRATK(Nle)L-NH2 + H2O
Ac-SNKTRIDEANQ + RATK(Nle)L-NH2
-
-
-
-
?
Ac-SNKTRIDEANQRATKML-NH2 + H2O
Ac-SNKTRIDEANQ + RATKML-NH2
-
-
-
?
Ac-SNKTRIDEANQRCTKML-NH2 + H2O
Ac-SNKTRIDEANQ + RCTKML-NH2
-
-
-
?
Ac-SNKTRIDECNQRATKML-NH2 + H2O
Ac-SNKTRIDECNQ + RATKML-NH2
-
-
-
?
biotin-KGSNRTRIDQGNQRATRXLGGK-biotin + H2O
?
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the catalytic activity resides on the light chains of the toxin molecule
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-
?
LQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDD + H2O
LQQTQAQVDEVVDI + MRVNVDKVLERDQK + LSELDD
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the vesicle-associated membrane protein, VAMP, sequence-derived peptide is a substrate of BoNT serotype D light chain
-
-
?
LSELDDRADALQAGASQFETSAAKLKRKYWWKNLK + H2O
LSELDDRADALQAGASQ + FETSAAKLKRKYWWKNLK
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the vesicle-associated membrane protein, VAMP, sequence-derived peptide is a substrate of BoNT serotype B light chain
-
-
?
membrane-anchored SNARE + H2O
?
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host membrane-anchored SNARE, proteolytically cleaved by BoNT/C
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-
?
Nutide + H2O
?
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i.e. FITC(bA)T(dR)IDQANQRAT(K/DABCYL)(Nle)-amide
-
-
?
Recombinant glutathione S-methyltransferase VAMP-2 fusion protein + H2O
Hydrolyzed recombinant glutathione S-methyltransferase VAMP-2 fusion protein
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-
2 proteolytic fragments, MW 36000 and MW 6000
?
Sb-Snc2p fusion protein + H2O
?
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a recombinant chimeric SNARE protein where a portion of neuronal synaptobrevin, Sb, is fused to Snc2p, a Sb ortholog required for protein secretion from yeast cells
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-
?
SNAP-23 + H2O
?
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a nonneuronal SNARE protein, that mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. SNAP23 is cleaved by an engineered BoNT/E light chain, LC/E K224D. Molecular modeling of the enzyme-substrate complex using the crystal structure of LC/E, Protein Data Bank ID 3d3x, overview
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-
?
SNAP-25 peptide (141-206) + H2O
?
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the minimal size of SNAP-25 known to retain full activity as a BoNT/A substrate is the C-terminal 66-mer peptide, residues 141-206, with both exosites
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-
?
SNAP-25-derived peptide + H2O
?
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i.e. HA-tagged SNAP25(141-206) or HA-tagged mutant SNAP25(141-206)-R198A, substrate of light chains of BoNT/A1, BoNT/A2, BoNT/A3, and BoNT/A4
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-
?
SNAP25(187-203) + H2O
?
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i.e. soluble N-ethylmaleimide-sensitive factor attachment protein 25, substrate fragmnent containing residues 87-203
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-
?
SNAPEtide + H2O
?
substrate for subtype BoNT/E
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-
?
SNARE-protein + H2O
?
-
soluble NSF-attachment protein receptor
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?
SNKTRIDEAAQRATKML + H2O
SNKTRIDEAAQ + RATKML
-
synthetic peptide substrate
-
?
SNKTRIDEANBRATKML + H2O
SNKTRIDEANB + RATKML
-
synthetic peptide substrate
-
?
SNKTRIDEANNRATKML + H2O
SNKTRIDEANN + RATKML
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synthetic peptide substrate
-
?
SNKTRIDEANQRABKML + H2O
SNKTRIDEANQ + RABKML
-
synthetic peptide substrate
-
?
SNKTRIDEANQRASKML + H2O
SNKTRIDEANQ + RASKML
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATAML + H2O
SNKTRIDEANQ + RATAML
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATK + H2O
SNKTRIDEANQ + RATK
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKAL + H2O
SNKTRIDEANQ + RATKAL
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKM + H2O
SNKTRIDEANQ + RATKM
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKXL + H2O
SNKTRIDEANQ + RATKXL
-
synthetic peptide substrate
-
?
SNKTRIDEANQRBTKML + H2O
SNKTRIDEANQ + RBTKML
-
synthetic peptide substrate
-
?
SNKTRIDEBNQRATKML + H2O
SNKTRIDEBNQ + RATKML
-
synthetic peptide substrate
-
?
SNKTRINEAAQRATKML + H2O
SNKTRINEAAQ + RATKML
-
synthetic peptide substrate
-
?
SNRTRIDEANK(Dnp)RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML + H2O
SNRTRIDEANK(Dnp) + RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML
synaptosome-associated protein SNAP-25 + H2O
hydrolyzed synaptosome-associated protein SNAP-25
-
-
-
-
?
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADAL + H2O
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ + KLSELDDRADAL
VAMP2 peptide + H2O
?
-
a synthetic peptide substrate representing amino acid residues 60-94 of the intracellular vesicle associated membrane protein 2, i.e. VAMP2, recombinant GST fusion protein and commercial preparation as substrates with equal activity for BONT/B
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-
?
vesicle-associated membrane protein VAMP + H2O
?
-
BoNT F cleaves VAMP between residues Q58 and K59. The minimum substrate is a peptide containing VAMP residues 32-65, which includes only one of the two VAMP structural motifs thought to be required for botulinum substrate recognition. BoNT F exhibits a strict requirement for residues D57 (P2), K59 (P1'), and L60 (P2'), but peptides containing substitutions for R56 (P3), Q58 (P1), and S61 (P3') are cleaved. Therefore, the P2, P1', and P2'?residues of VAMP are of paramount importance for BoNT F substrate recognition near the scissile bond
-
-
?
vesicle-associated membrane protein-2 mutant D51A + H2O
?
-
the enzyme cleaves the mutant substrate with about 10fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant E41A + H2O
?
-
the enzyme cleaves the mutant substrate with about 80fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant E55A + H2O
?
-
the enzyme cleaves the mutant substrate with about 750fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant K52A + H2O
?
-
the enzyme cleaves the mutant substrate with about 20fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant N49A + H2O
?
-
the enzyme cleaves the mutant substrate with about 10fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant Q58A + H2O
?
-
the enzyme cleaves the mutant substrate with about 25fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant R31A + H2O
?
-
the enzyme cleaves the mutant substrate with about 20fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant R56A + H2O
?
-
the enzyme cleaves the mutant substrate with about 4000fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant V50A + H2O
?
-
the enzyme cleaves the mutant substrate with about 50fold lower efficiency compared to the wild type substrate
-
-
?
Ac-RGSNKPKIDAGNQRATRXLGGR-NH2 + H2O
Ac-RGSNKPKIDAGNQR + ATRXLGGR-NH2
-
-
-
?
Ac-RGSNKPKIDAGNQRATRXLGGR-NH2 + H2O
Ac-RGSNKPKIDAGNQR + ATRXLGGR-NH2
-
-
-
?
Ac-RGSNKPKIDAGNQRATRXLGGR-NH2 + H2O
Ac-RGSNKPKIDAGNQR + ATRXLGGR-NH2
-
-
-
?
cytosolic SNARE + H2O
?
-
host cytosolic SNARE, i.e. soluble NSF attachment protein receptor, a central helical protein-conducting channel, which chaperones the protease across host endosomes, modelling, overview. Sequence-specific claveage by the endoprotease activity of the BoNT light chains
-
-
?
cytosolic SNARE + H2O
?
-
host cytosolic SNARE, i.e. soluble NSF attachment protein receptor, a central helical protein-conducting channel, which chaperones the protease across host endosomes, modelling, overview. Sequence-specific claveage by the endosprotease activity of the BoNT light chains. Enzyme-substrate complex, overview
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
neurotoxin binds specifically to nerve cells, botulin neurotoxin-receptors are located on the motor neuron plasmalemma at neuromuscular junctions, neurotoxin binds via protein and lipid interaction, after binding it is internalized inside vesicles of unknown nature
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
involved in limited hydrolysis of proteins of the neuroexocytosis apparatus, blocks release of neurotransmitter acetylcholine at neuromuscular junction
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
causing flaccid paralysis, in contrast to spastic paralysis caused by EC 3.4.24.68, three functionally distinct domains: domain L blocks neuroexocytosis, domain HN governs cell penetration, domain HC responsible for neurospecific binding
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
neurotoxin binds specifically to nerve cells, botulin neurotoxin-receptors are located on the motor neuron plasmalemma at neuromuscular junctions, neurotoxin binds via protein and lipid interaction, after binding it is internalized inside vesicles of unknown nature
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
involved in limited hydrolysis of proteins of the neuroexocytosis apparatus, blocks release of neurotransmitter acetylcholine at neuromuscular junction
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
causing flaccid paralysis, in contrast to spastic paralysis caused by EC 3.4.24.68, three functionally distinct domains: domain L blocks neuroexocytosis, domain HN governs cell penetration, domain HC responsible for neurospecific binding
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
neurotoxin binds specifically to nerve cells, botulin neurotoxin-receptors are located on the motor neuron plasmalemma at neuromuscular junctions, neurotoxin binds via protein and lipid interaction, after binding it is internalized inside vesicles of unknown nature
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
involved in limited hydrolysis of proteins of the neuroexocytosis apparatus, blocks release of neurotransmitter acetylcholine at neuromuscular junction
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
causing flaccid paralysis, in contrast to spastic paralysis caused by EC 3.4.24.68, three functionally distinct domains: domain L blocks neuroexocytosis, domain HN governs cell penetration, domain HC responsible for neurospecific binding
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
neurotoxin binds specifically to nerve cells, botulin neurotoxin-receptors are located on the motor neuron plasmalemma at neuromuscular junctions, neurotoxin binds via protein and lipid interaction, after binding it is internalized inside vesicles of unknown nature
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
causing flaccid paralysis, in contrast to spastic paralysis caused by EC 3.4.24.68, three functionally distinct domains: domain L blocks neuroexocytosis, domain HN governs cell penetration, domain HC responsible for neurospecific binding
-
-
?
Proteins of neuroexocytosis apparatus + H2O
?
-
-
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C
-
-
?
SNAP-25 + H2O
?
-
-
-
-
?
SNAP-25 + H2O
?
P10845
BoNT/A-LC is a Zn(II)-dependent metalloprotease that blocks the release of acetylcholine at the neuromuscular junction by cleaving SNAP-25, one of the SNARE proteins required for exocytosis
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosomal associated protein of 25 kDa
-
-
?
SNAP-25 + H2O
?
P10845
i.e. synaptosomal associated protein of 25 kDa
-
-
?
SNAP-25 + H2O
?
serotypes BoNT/A and BoNT/E cleave SNAP-25 at distinct sites, BoNT/E blocks neurotransmission faster and more potently
-
-
?
SNAP-25 + H2O
?
-
the potent botulinum neurotoxin inhibits neurotransmitter release at cholinergic nerve terminals, causing a descending flaccid paralysis characteristic of the disease botulism
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosomal associated protein of 25 kDa, all botulinus neurotoxin serotypes cleave the substrate at a unique peptide bond, BoNT/A cleaves SNAP-25 between residues Gln197 and Arg198. Phe194, Ile161, and Asp370 form the S1' subsite responsible for binding the P1' arginine side chain of SNAP-25, overview
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosomal associated protein of 25 kDa, human substrate, substrate peptide fragment products, overview
-
-
?
SNAP-25 + H2O
?
-
serotype BoNT/C1-LC exhibits dual specificity toward both syntaxin and SNAP-25, in contrast to other serotypes, due to a distinct pocket S1' near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin, activity of the serotype C enzyme BoNT/C1-LC with diverse SNAp-25 substrate mutants, overview
-
-
?
SNAP-25 + H2O
?
substrate is a recombinant GFP-SNAP-25-(134206)-His6 fusion protein
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosome-associated protein, BoNT/A requires two extended exosites for optimal substrate binding and recognition of its intracellular target SNAP-25
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosomal-associated protein, substrate of BoNT/A
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein
-
-
?
SNAP-25 + H2O
?
P10845
i.e. 25-kDa synaptosome-associated protein
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, a substrate of BoNT/A light chain
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, BoNT/A
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, is involved in acetylcholine release at the neuromuscular junction
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, a plasma membrane-associated protein, proteolytically cleaved by BoNT types A, C, and E
-
-
?
SNAP-25 + H2O
?
-
a neuronal SNARE protein, cleaved by an engineered BoNT/E light chain, LC/E K224D
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosomal-associated protein, substrate of BoNT serotypes A and E
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, design and construction of a lab-on-a-chip for the in vitro detection of BoNT-A activity using an assay that measures cleavage of the fluorescence-labeled peptide substrate specific for BoNT-A by the toxin light chain, detection by Foerster resonance energy transfer, FRET, fluorescence, method development and evaluation, overview. The peptide substrate is labeled with internally labeled with the FRET pair fluorescein-thiocarbamoyl, FITC, and 4-(dimethyla-minoazo)benzene-4-carboxylic acid, DABCYL, or with FITC only for positive control
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, development of a BoNT/A-specific assay method, overview. Usage of BoNT/A cleavage-sensitive antibodies that only interact with full-length SNAP-25, the molecular target of the BoNT/A serotype. These antibodies exhibit high specificity for full-length SNAP-25, allowing the BoNT/A-mediated proteolysis of this protein to be measured in diverse assay formats, e.g. ELISA and immunofluorescent assay methods, detailed overview
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, substrate of light chains of BoNT/A1, BoNT/A2, BoNT/A3, and BoNT/A4
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, the Michaelis complex involves an extensive network of binding interactions ranging from the active site to the opposite surface of the BoNT/A. In the complex, the N-terminal residues of SNAP-25 147-167 form an alpha-helix, imbedded in the rear surface of BoNT/A while the C-terminal residues 201-204 form a distorted beta-strand, and the spanning residues are mostly extended
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, truncated version of SNAP-25
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein. The BoNT/E-truncated C-terminal peptide of SNAP-25 is CDMGNEIDTQNRQIDR
-
-
?
SNAP-25 + H2O
?
-
17-residue C-terminal peptide corresponding to residue 187-203 of SNAP-25
-
-
?
SNAP-25 + H2O
?
-
cleaved by the light chains of subtypes BoNT/A and BoNT/E
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C
-
-
?
SNAP25 + H2O
?
-
i.e. soluble N-ethylmaleimide-sensitive factor attachment protein 25, the enzyme cleaves SNARE proteins, i.e. SNAP receptor proteins, to elicit flaccid paralysis by inhibiting neurotransmitter-carrying vesicle fusion to the plasma membrane of peripheral neurons, overview
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, located at the host synaptic membrane, serotype E toxin cleaving SNAP25 prevents assembly of the synaptic fusion complex and therefore the fusion of the acetylcholine-containing vesicle and the synaptic membrane
-
-
?
SNAP25 + H2O
?
-
zinc-endopeptidase activity of the N-terminal light chain of BoNT/A on synaptosome-associated protein-25 kDa of the SNARE complex
-
-
?
SNAP25 + H2O
?
-
i.e. soluble N-ethylmaleimide-sensitive factor attachment protein 25, recombinant GST-tagged wild-type and mutant D193A, R198A, R198E, and I171A substrates, full-length and truncated substrate, SNAP25 initially binds along the belt region of BoNT/A, which aligns the P5 residue to the S5 pocket at the periphery of the active site, binding site structures, reaction mechanism, molecular modeling of the LC/A active site domain, overview
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosomal-associated protein of 25 kDa, SNAP25 with varying peptide length, substrate specificity of BoNT/C1, e.g. 17mer peptide corresponding to residues 187-203 of SNAP-25 is a substrate for BoNT/C1 (1-430), importance of remote exosites in BoNT/C1 required for activity, assay optimization, overview
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, located at the host synaptic membrane
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, located at the host synaptic membrane, serotype E toxin cleaving SNAP25 prevents assembly of the synaptic fusion complex and therefore the fusion of the acetylcholine-containing vesicle and the synaptic membrane
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, located at the host synaptic membrane
-
-
?
SNAPtide + H2O
?
-
i.e. SNAPtide, as recombinant human SNAP25bHA protein expressed in Escherichia coli
-
-
?
SNKTRIDEANQRATKML + H2O
SNKTRIDEANQ + RATKML
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKML + H2O
SNKTRIDEANQ + RATKML
-
the SNAP-25 peptide is a BoNT serotype A light chain substrate, a 17-residue synthetic peptide corresponding to residues 187 to 203 of SNAP-25. Serotype C1 cleaves the serotype A substrate at a bond separated by only one residue compared to serotype A
-
-
?
SNRTRIDEANK(Dnp)RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML + H2O
SNRTRIDEANK(Dnp) + RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML
-
a SNAP-25 peptide, residues 187-203, substrate BoNT/A LC FRET-based assay
-
-
?
SNRTRIDEANK(Dnp)RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML + H2O
SNRTRIDEANK(Dnp) + RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML
P10845
a synthetic fluorogenic peptide substrate of BoTxA/LC, representing amino acid residues 187-203 of SNAP25, a cleavage site of the enzyme
-
-
?
synaptobrevin + H2O
?
-
synaptic vesicle-associated membrane protein, neurotoxin responsible for human and animal botulism
-
-
?
synaptobrevin + H2O
?
-
a vesicle-associated membrane protein, also known as VAMP, the most abundant SV entity, proteolytically cleaved by BoNT types B, D, F, and G
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Ala-+-Ala-Lys
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Gln-Lys-+-Leu-Ser
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes D, F or G
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying synaptobrevin/VAMP-2
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying Val76 instead of Gln76 is not hydrolyzed by serotype BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
highly specific neurotoxins
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Gln-+-Phe-Glu (at the same site as the tetanus neurotoxin)
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at -Asp-Gln-+-Lys-Leu-, serotype BoNT/G: cleavage at Ala83-Ala84 (VAMP-1), Ala81-Ala82 (VAMP-2)
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Gln76-Phe77
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Ala-+-Ala-Lys
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Gln-Lys-+-Leu-Ser
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes D, F or G
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
no substrate of serotype BoNT/A or E
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying synaptobrevin/VAMP-2
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
both isoforms are cleaved at the same rate
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying Val76 instead of Gln76 is not hydrolyzed by serotype BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
highly specific neurotoxins
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Gln-+-Phe-Glu (at the same site as the tetanus neurotoxin)
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at -Asp-Gln-+-Lys-Leu-, serotype BoNT/G: cleavage at Ala83-Ala84 (VAMP-1), Ala81-Ala82 (VAMP-2)
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Ala-+-Ala-Lys
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Gln-Lys-+-Leu-Ser
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes D, F or G
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying synaptobrevin/VAMP-2
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying Val76 instead of Gln76 is not hydrolyzed by serotype BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
highly specific neurotoxins
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Gln-+-Phe-Glu (at the same site as the tetanus neurotoxin)
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/F: cleavage at Gln-Lys
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes D, F or G
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/D: cleavage at Lys61-Leu62
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying synaptobrevin/VAMP-2
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
both isoforms are cleaved at the same rate
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying Val76 instead of Gln76 is not hydrolyzed by serotype BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
highly specific neurotoxins
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/D: cleavage at Lys61-Leu62
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying synaptobrevin/VAMP-2
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/F: cleavage at Gln-Lys
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
both isoforms are cleaved at the same rate
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
highly specific neurotoxins
-
-
?
synaptobrevin-2 + H2O
?
-
cleaves in the same location as that cleaved by BoNT/F proteolytic F toxin of Clostridium botulinum
-
-
?
synaptobrevin-2 + H2O
?
-
cleaves in the same location as that cleaved by BoNT/F proteolytic F toxin of Clostridium botulinum
-
-
?
Synaptosome-associated protein + H2O
?
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
?
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
?
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
?
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A and E
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro, in isolated synaptosomes
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asn-Gln-+-Arg-Ala
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro and in injected Aplysia neurons
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asp-Arg-+-Ile-Met
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
MW 25000
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
highly specific neurotoxins
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A and E
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro, in isolated synaptosomes
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asn-Gln-+-Arg-Ala
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/E: cleavage at Arg180-Ile181
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
no substrate of serotype BoNT/G
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro and in injected Aplysia neurons
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asp-Arg-+-Ile-Met
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
native and recombinant protein
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
MW 25000
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Gln197-Arg198
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A and E
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro, in isolated synaptosomes
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asn-Gln-+-Arg-Ala
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro and in injected Aplysia neurons
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asp-Arg-+-Ile-Met
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
MW 25000
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A and E
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
-
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
hydrolyzed by BoNT/A, BoNT/E and BoNT/CI
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
significant structural changes near the toxin's catalytic pocket upon substrate binding, probably serving to render the protease competent for catalysis
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
-
-
?
Syntaxin + H2O
?
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
Syntaxin + H2O
?
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
Syntaxin + H2O
?
-
serotype BoNT/C1-LC exhibits dual specificity toward both syntaxin and SNAP-25, in contrast to other serotypes, due to a distinct pocket S1' near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin
-
-
?
Syntaxin + H2O
?
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADAL + H2O
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ + KLSELDDRADAL
-
-
-
?
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADAL + H2O
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ + KLSELDDRADAL
Clostridium baratii CNM1212/11
-
-
-
?
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADAL + H2O
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ + KLSELDDRADAL
-
-
-
?
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADAL + H2O
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ + KLSELDDRADAL
Clostridium botulinum H078-01
-
-
-
?
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADAL + H2O
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ + KLSELDDRADAL
-
-
-
?
VAMP + H2O
?
-
i.e. neuronal vesicle-associated membrane protein, substrate of BoNT/B, /D, /F, and /G
-
-
?
VAMP + H2O
?
-
i.e. vesicle associated membrane protein or synaptobrevin, BoNT/B, and BoNT/F
-
-
?
VAMP + H2O
?
i.e. vesicle-associated membrane protein/synaptobrevin
-
-
?
VAMP + H2O
?
-
i.e. vesicle-associated membrane protein/synaptobrevin, substrate of BoNT/B, /D, /F, /G, and /C
-
-
?
VAMP + H2O
?
-
i.e. neuronal vesicle-associated membrane protein, substrate of BoNT/B, /D, /F, and /G
-
-
?
VAMP + H2O
?
i.e. vesicle-associated membrane protein/synaptobrevin, activity with substrate fragments and mechanism of substrate recognition of BoNT F, overview. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis. In exosite 2, BoNT F Arg133 has a dominant role in allowing docking of the V1-SNARE motif, by interacting with the main chain of VAMP Val43, the side chain of VAMP Glu41 and with a water that interacts with other main chain residues of VAMP. The VAMP E41A mutant is 470% cleavage resistant, as compared to the native VAMP
-
-
?
VAMP + H2O
?
-
i.e. neuronal vesicle-associated membrane protein, substrate of BoNT/B, /D, /F, and /G
-
-
?
VAMP 2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2
-
-
?
VAMP 2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2, with BoNT/B light chain
-
-
?
VAMP-1 + H2O
?
-
subtype BoNT/D does not cleave human VAMP-1 efficiently
-
-
?
VAMP-1 + H2O
?
-
subtype BoNT/D does not cleave human VAMP-1 efficiently
-
-
?
VAMP-2 + H2O
?
-
initial substrate recognition is mediated through sequential binding of VAMP-2 to the B1, B2 and B3 pockets in LC/F (light chain of BoNT serotype F), which directed VAMP-2 to the active site of LC/F and stabilized the active site substrate recognition, where the P2, P1' and P2' sites of VAMP-2 are specifically recognized by the S2, S1' and S2' pockets of LC/F to promote substrate hydrolysis
-
-
?
VAMP-2 + H2O
?
-
cleaved by the light chains of subtypes BoNT/B, BoNT/T, BoNT/D, and BoNT/F
-
-
?
VAMP2 + H2O
?
-
i.e. intracellular vesicle associated membrane protein 2
-
-
?
VAMP2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2
-
-
?
VAMP2 + H2O
?
-
human VAMP2 substrate, i.e. vesicle-associated membrane protein 2
-
-
?
VAMP2 + H2O
?
-
i.e. vesicle-associated membrane protein 2 or synaptobrevin-2, with BoNT/B light chain. BoNT/B HT exhibits little ability to cleave its substrate VAMP-2, when its LC and HC subunits are held together by a disulfide bond
-
-
?
VAMPTide + H2O
?
-
a VAMP-2-derived peptide substrate, modified with FRET, with BoNT/B light chain
-
-
?
VAMPTide + H2O
?
substrate for subtype BoNT/B
-
-
?
vesicle-associated membrane protein-1 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-1 + H2O
?
the enzyme suybtype BoNT/X cleaves vesicle-associated membrane protein-1 with a 10times higher efficiency than subtype BoNT/B and tetanus neurotoxin
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Gln58-Lys59
-
-
?
vesicle-associated membrane protein-2 + H2O
?
Clostridium baratii CNM1212/11
cleavage at Gln58-Lys59
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Gln58-Lys59
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
cleavage at Leu54-Glu55
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
cleavage between L54 and E55
-
-
?
vesicle-associated membrane protein-2 + H2O
?
Clostridium botulinum BCA10-7060
-
cleavage between L54 and E55
-
-
?
vesicle-associated membrane protein-2 + H2O
?
Clostridium botulinum H078-01
cleavage at Gln58-Lys59
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Gln58-Lys59
-
-
?
vesicle-associated membrane protein-3 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-4 + H2O
?
cleavage at Lys87-Ser88
-
-
?
vesicle-associated membrane protein-5 + H2O
?
cleavage at Arg40-Ser41
-
-
?
additional information
?
-
-
no hydrolysis of short peptides spanning the respective cleavage sites of the target proteins
-
-
?
additional information
?
-
-
the heavy chain mediates the binding of the toxin with ganglioside and glycoprotein receptors at the neuronal surface, followed by toxin entry by means of receptor-mediated endocytosis. It mediates the translocation of the light chain into the neuronal cytosol, where it functions as a Zn2+-dependent endoprotease
-
-
?
additional information
?
-
-
development and evaluation of in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors, development of FRET substrates, overview
-
-
?
additional information
?
-
-
catalytic activity requires reduction of the single interchain disulfide bond of the neurotoxin
-
-
?
additional information
?
-
-
catalytic activity requires reduction of the single interchain disulfide bond of the neurotoxin
-
-
?
additional information
?
-
-
no hydrolysis of short peptides spanning the respective cleavage sites of the target proteins
-
-
?
additional information
?
-
-
no hydrolysis of short peptides spanning the respective cleavage sites of the target proteins
-
-
?
additional information
?
-
-
activating protease activity is localized on light or L-chain of neurotoxin
-
-
?
additional information
?
-
-
the clostridial neurotoxins differ from other proteases in the recognition of the tertiary structure of the target rather than the sequence of the peptide bond to be cleaved
-
-
?
additional information
?
-
-
neuroparalytic activity tested by intravenous injection into Balb/c mice
-
-
?
additional information
?
-
-
able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by flaccid paralysis
-
?
additional information
?
-
-
only mammalian proteins, SNAP-25 from Drosophila sp. and Torpedo sp. are no substrates
-
?
additional information
?
-
-
undergoes autocatalytic proteolytic processing and fragmentation
-
?
additional information
?
-
-
BoNTs are the most toxic proteins known with mouse LD50 values in the range of 1-5 ng/kg. They are responsible for the pathophysiology of botulism. BoNTs enter peripheral cholinergic nerve terminals, where they cleave one or two of the three core proteins of the neuroexocytosis apparatus and elicit persistent but reversible inhibition of neurotransmitter release
-
-
?
additional information
?
-
-
botulinum neurotoxins are a group of proteins produced by different strains of Clostridium botulinum, that are responsible for botulism disease
-
-
?
additional information
?
-
-
boutulinum neurotoxin is a potent inhibitor of neuroexocytosis. Organization and regulation of the neurotoxin gene. The botulinum neurotoxin and non-toxic protein genes are organized in two polycistronic operons transcribed in opposite orientation
-
-
?
additional information
?
-
-
BoNTs bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs, soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors, which constitute part of the synaptic vesicle fusion machinery, botulinum neurotoxins cause the neuroparalytic syndrome of botulism, BoNTs are biological hazard to humans and a serious potential bioweapon threat with a lethal dose of 1 ng/kg body weight
-
-
?
additional information
?
-
-
clostridial neurotoxins are the causative agents of the neuroparalytic diseases botulism and tetanus blocking neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors, SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery
-
-
?
additional information
?
-
-
intraglandular injection of botulinum toxin leads to a transient denervation of the submandibular gland and this is associated with reduced salivary secretion in Wistar rats, which may be due to glandular denervation induced by the inhibition of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors involved in acetylcholine release at the neuroglandular junction and also specially inhibition of those involved in exocytosis of the granula of the acinar cells. Cell organelles and secretory granula show a clear atrophy of the acini, which is more prominent in glands injected with the combination of BoNT/A and B, overview
-
-
?
additional information
?
-
-
LC-mediated proteolysis of SNARE proteins and consequent inhibition of synaptic vesicle fusion to the presynaptic membrane of human motor neurons are responsible for flaccid paralysis associated with botulism
-
-
?
additional information
?
-
-
the cytopathic effect of C2I-C2IIa toxin, e.g. on human HeLa or colon cancer Caco-2 cells, or Vero cells, is higher for the single components compared to the complex
-
-
?
additional information
?
-
-
the enzyme causes neuroparalysis by blocking neurotransmitter release at the neuromuscular junctions
-
-
?
additional information
?
-
-
the neurotoxic enzyme causes the neuroparalytic illness botulism in humans acting as an endopeptidase which cleaves proteins that are necessary for acetylcholine exocytosis, botulinum toxin affets the strength-duration time constant in patients, the toxin acts on the Na+/K+ pump activity, overview
-
-
?
additional information
?
-
-
the proteolytically activated 60 kDa C2II binding component is essential for C2I transport into target cells involving especially amino acids Glu399, Asp426, and Phe428, it forms heptameric channels into membranes that are cation-selective and can be blocked by chloroquine and related compounds
-
-
?
additional information
?
-
P10845
the seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific SNARE complex proteins and block the release of neurotransmitters causing flaccid paralysis and are considered potential bioweapons, botulinum neurotoxin type A is the most potent among the clostridial neurotoxins
-
-
?
additional information
?
-
-
the seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific SNARE complex proteins and block the release of neurotransmitters causing flaccid paralysis and are considered potential bioweapons, botulinum neurotoxin type A is the most potent among the clostridial neurotoxins
-
-
?
additional information
?
-
the seven serotypes A-G potently block neurotransmission by binding to presynaptic receptors, undergoing endocytosis, transferring to the cytosol, and inactivating proteins essential for vesicle fusion, overview
-
-
?
additional information
?
-
-
toxicity in mice of full-length, single-nicked, and double-nicked enzyme forms, overview
-
-
?
additional information
?
-
-
development of a rapid assay method to distiguish the enzyme serotypes A, B, E, F, and G, substrate requirements of the different serotypes, overview
-
-
?
additional information
?
-
-
Glu224 and Glu262 are structurally essential for activity, structure-function relationship, overview
-
-
?
additional information
?
-
-
identification of active site and surrounding residues involved in substrate recognition and catalysis of BoNT/A, overview
-
-
?
additional information
?
-
-
LC-mediated proteolysis of soluble N-ethylmaleimide-sensitive factor attachment protein receptor, i.e. SNARE, proteins, complex reaction mechanism, overview
-
-
?
additional information
?
-
-
the catalytic component of the clostridial neurotoxins is their light chain, a Zn2+ endopeptidase, active site structure of serotype C1, substrate and cleavage site specificity of serotypes, overview
-
-
?
additional information
?
-
-
the enzyme is a binary toxin, which is composed of two separate proteins, the enzyme component C2I is an ADP-ribosyltransferase which modifies G-actin of eukaryotic cells, while the proteolytically activated binding/translocation component C2IIa forms ring-shaped heptamers, which bind to cell receptors and mediate the transport of C2I into the cytosol of target cells. Receptor-bound C2IIa serves as a docking platform for C2I on the cell surface, following assembly of C2I, the toxin complex is taken up via receptor-mediated endocytosis, and finally, C2IIa facilitates translocation of C2I from acidic endosomes into the cytosol, the preformed C2 toxin complex ADP-ribosylates actin in vitro and induces cell rounding, overview
-
-
?
additional information
?
-
-
the neurotoxin serotypes show distinct substrate specificities, overview
-
-
?
additional information
?
-
-
the the receptor-binding domain of botulinum neurotoxin serotype B binds to the luminal domain of synaptotagmin II, i.e. Syt-II, interaction occurs at both neutral and acidic endosomal pH, residues Glu44 to Lys60 become structured with residues Phe47 to Ile58 forming an alpha-helix, the HCB-Syt-II complex is stabilized by extensive intermolecular interactions involving two pronounced pockets on the HCB surface, structure, overview, high selectivity of BoNT/B among synaptotagmin I and II isoforms
-
-
?
additional information
?
-
BoNT E first binds to GT1b on the presynaptic membrane, like all other BoNTs. In BoNT B, the sialic acid of the sialyllactose that partly mimics GT1b binds in a shallow cavity formed by Trp1261 and His1240,12 and interacts with Tyr1262 and His1240, binding mode, overviewThe GT1b binding site in BoNT E is similar to those in other BoNTs and tetanus neurotoxin
-
-
?
additional information
?
-
-
BoNT E first binds to GT1b on the presynaptic membrane, like all other BoNTs. In BoNT B, the sialic acid of the sialyllactose that partly mimics GT1b binds in a shallow cavity formed by Trp1261 and His1240,12 and interacts with Tyr1262 and His1240, binding mode, overviewThe GT1b binding site in BoNT E is similar to those in other BoNTs and tetanus neurotoxin
-
-
?
additional information
?
-
-
BoNT serotypes bind to structure of ganglioside GT1b receptors, structure and binding specificities, modelling, overview
-
-
?
additional information
?
-
-
BoNT/A and BoNT/B bind a synaptic vesicle protein complex from synaptic vesicles, interactions of BoNT and host neuronal receptors, overview. Binding and entry of BoNTs at the neuromuscular junction, BoNT/A associates with the presynaptic membrane of alpha-motor neurons through interactions with oligosaccharides such as ganglioside GT1b, structure-function, modelling, overview
-
-
?
additional information
?
-
-
BoNT/A binds to peripheral cholinergic nerve terminals, causing their inhibition, rapidly and with high specificity via its receptor binding, heavy chain domain termed HC. BoNT/A interacts specifically with polysialogangliosides and with a luminal loop of the synaptic vesicle protein SV2 via the C-terminal half of HC, while the N-terminal half of it binds to sphingomyelin-enriched membrane microdomains and shows defined interaction with phosphatidylinositol phosphates, that might play a role in the correct positioning of the toxin for the subsequent low pH-driven membrane insertion of translocation domain sHN. Molecular modelling of Hc-N/A membrane binding, overview
-
-
?
additional information
?
-
BoNTs bind motor neurons via ganglioside-protein dual receptors, i.e. two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core, HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2, structure-function properties of BoNT/F host receptor interactions, dual receptors for BoNT/F, overview. Deglycosylation of glycoproteins disrupts the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, is unaffected. Mutations within the putative ganglioside binding pocket of HCR/F decrease binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons, overview
-
-
?
additional information
?
-
-
BoNTs exert their neurotoxic effect by a multistep mechanism: binding, internalization, membrane translocation, intracellular traffic, and proteolytic degradation of target. The protein receptors are SV2 for BoNT/A, BoNT/E, and BoNT/F, and synaptotagmin I and II for BoNT/B and BoNT/G. BoNTs enter sensitive host cells via receptor-mediated endocytosis, detailed overview. The protease is chaperoned across host endosomes, DELTApH of early endosomes is finely tuned to elicit drastic conformational changes, leading to the insertion of BoNT into the membrane, while it is auspiciously set to interrupt further processing in the harsh acidic conditions existent inside lysosomes. HC dictates the target cell specificity and, during cell binding and intracellular traffic, serves to chaperone the light chain and HN, which ensures that partial unfolding of the light chain is concomitant with HN channel formation, thereby promoting productive light chain translocation
-
-
?
additional information
?
-
botulinum neurotoxin binds host peripheral neurons at the neuromuscular junction through a dual-receptor mechanism that includes interactions with ganglioside and protein receptors. The receptor identities vary depending on BoNT serotype. BoNT/B and BoNT/G bind the luminal domains of synaptotagmin I and II, homologous synaptic vesicle proteins, structure analysis of BoNT/G binding to Syt andGT1b, overview
-
-
?
additional information
?
-
-
design of BoNT A or B H-chain peptides for localizing BoNT/A binding regions to mouse brain synaptosomes
-
-
?
additional information
?
-
P10845
ganglioside GT1b is considered as BoNT/A receptor at nerve cells and can bind to the C-terminal end of the heavy chain
-
-
?
additional information
?
-
-
ganglioside GT1b is considered as BoNT/A receptor at nerve cells and can bind to the C-terminal end of the heavy chain
-
-
?
additional information
?
-
-
sialic acid-dependent binding is required for the transcytosis of serotype D botulinum neurotoxin and toxin complex L-TC in rat intestinal epithelial cell line IEC-6, mechanism, overview. HA-33 molecules play an important role in the effective binding of D-4947 L-TC to Caco-2 cells
-
-
?
additional information
?
-
-
the BoNT light chain domain is the Zn-dependent metalloprotease, that cleaves specific proteins that prevent acetylcholine release. BoNT shows endoproteolytic activity on one of the three SNARE proteins, i.e. soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins. The BoNT serotypes all show distinct cleavage sites on the SNARE substrates
-
-
?
additional information
?
-
-
the catalytic light chains of BoNTs, BoNT-LC, recognize extended regions of their substrates for cleavage
-
-
?
additional information
?
-
-
the heavy chain mediates the binding of the toxin with ganglioside and glycoprotein receptors at the neuronal surface, followed by toxin entry by means of receptor-mediated endocytosis. It mediates the translocation of the light chain into the neuronal cytosol, where it functions as a Zn2+-dependent endoprotease
-
-
?
additional information
?
-
-
the toxin light chain, LC, is a zinc-dependent endopeptidase that cleaves soluble N-ethylmaleimide-sensitive fusion proteins, SNARE, located at nerve endings
-
-
?
additional information
?
-
active site structure, Tyr351 is close to both nucleophilic water and catalytic zinc, overview
-
-
?
additional information
?
-
-
active site structure, Tyr351 is close to both nucleophilic water and catalytic zinc, overview
-
-
?
additional information
?
-
-
assay method measuring noradrenaline release in human neuronal SHSY-5Y cells
-
-
?
additional information
?
-
-
assay method measuring noradrenaline release in human neuronal SHSY-5Y cells
-
-
?
additional information
?
-
-
BoNT/E light chain mutant K224D does not cleave the SNARE proteins SNAP29 or SNAP47
-
-
?
additional information
?
-
-
development and evaluation of in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors, development of FRET substrates, overview
-
-
?
additional information
?
-
-
development of a fluorescence sandwich immunoassay for BoNT activity determination, using serotype BoNT/A, demonstration of its application in both 96-well plate- and bead-based assay formats, both involving a solid substrate, overview
-
-
?
additional information
?
-
-
development of an improved ultra-performance liquid chromatography product detection method, overview
-
-
?
additional information
?
-
-
development of Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A-G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples
-
-
?
additional information
?
-
-
development of internally quenched fluorescent substrates containing the fluorophore/repressor pair pyrenylalanine/4-nitrophenylalanine for a sensitive assay method. (pNO2-Phe) and (1-pyrenylalanine) are, respectively, introduced at positions 197 and 200 of the cleavable fragment, amino acids 187 to 203, of SNAP-25, with norleucine at position 202 [Nle202], which is acetylated at its N terminus and amidated at its C-terminus. Sensitivity is increased when the peptide sequence of the previous substrate is lengthened to account for exosite binding to BoNT/A, substrate specificity and assay optimization, overview
-
-
?
additional information
?
-
-
enzyme-substrate complex, detailed overview. BoNT/C is unique among the BoNTs, in that it cleaves both SNAP-25 and syntaxin, another plasma membrane-anchored SNARE
-
-
?
additional information
?
-
-
F1-40 is a mouse-derived, IgG1 monoclonal antibody that binds the light chain of BoNT serotype A and is used in a sensitive immunoassay for toxin detection, determination of binding epitopes, overview
-
-
?
additional information
?
-
-
feasibility of using the CFP-YFP pair with full-length SNAP-25 as a FRET-based substrate for BoNT/A in a cell-based assay or with the 66-mer peptide as a FRET substrate in an in vitro assay, optimization of FRET efficiency by use of fluorescent protein variants, CsY, CsYY or YsCsY, overview
-
-
?
additional information
?
-
-
functional assay of the toxin protease activity using a fluorogenic substrate. Development of a bead-based sandwich immunoassay for botulinum neurotoxin serotype A, BoNT/A, using a recombinant 50 kDa fragment of the BoNT/A heavy chain as a structurally valid simulant. Different anti-BoNT/A antibodies are attached to three different fluorescent, dye encoded flow cytometry beads for multiplexing. The assay is conducted in two formats: a manual microcentrifuge tube format and an automated fluidic system format. Flow cytometry detection is used for both formats, method evaluation, overview
-
-
?
additional information
?
-
-
recombinant BoNT/E fragment HC1163-1256 binds synaptotagmin and gangliosides, the expressed and purified HC1163-1256 protein retains a functionally active conformation
-
-
?
additional information
?
-
-
regions on BoNT/B that bind to blocking antibodies, synaptotagmin, or gangliosides, recognition pattern, overview
-
-
?
additional information
?
-
-
standard assay used to determine potency of clinical samples is the in vivo mouse bioassay, MBA, another possibilty is the primary rat spinal cord cells using RSC assay, that also permits sensitive and quantitative detection of BoNT/A, with usage of Sprague Dawley E15 rat pup spinal cords, Direct comparison of MBA and RSC assays, overview
-
-
?
additional information
?
-
-
substrate specificities of the BoNT light chain subtypes, overview. The LC subtypes perform autolytic cleavage. Each LC/A subtype possesses the di-tyrosine autocleavage site, which indicate that residues in addition to the cleavage site are necessary for autocleavage. Control LC, LC/A1 DYM, contains mutations to cleavage site residues, Y250A and Y251A, which abrogates autocatalysis in LC/A1
-
-
?
additional information
?
-
-
synaptosome capture assay for the different serotype BoNTs, synaptosome from rat brains, overview
-
-
?
additional information
?
-
-
usage of a single molecule assay of BoNT serotypes A and E light chain translocation through the heavy chain channel in neurons, and of BoNT intoxication assays, namely the mouse protection and the primary rat spinal cord cell assays
-
-
?
additional information
?
-
-
enzyme binding to the receptor synaptotagmin II is functionally related to the enzyme's toxic action
-
-
?
additional information
?
-
-
no activity with synaptosome-associated protein SNAP-25 and syntaxin
-
-
?
additional information
?
-
no activity with vesicle-associated membrane protein-7, vesicle-associated membrane protein-8, syntaxin 1, SNAP-25 and Sec22b
-
-
?
additional information
?
-
-
subtype BoNT/A6 enters cells more efficiently than other enzyme subtypes
-
-
?
additional information
?
-
-
the reduction of the disulfide bond is necessary for the optimum activity of the enzyme
-
-
?
additional information
?
-
Clostridium botulinum CDC41370
-
subtype BoNT/A6 enters cells more efficiently than other enzyme subtypes
-
-
?
additional information
?
-
Clostridium botulinum IBCA10-7060
-
no activity with synaptosome-associated protein SNAP-25 and syntaxin
-
-
?
additional information
?
-
Clostridium botulinum Osaka05
-
enzyme binding to the receptor synaptotagmin II is functionally related to the enzyme's toxic action
-
-
?
additional information
?
-
-
catalytic activity requires reduction of the single interchain disulfide bond of the neurotoxin
-
-
?
additional information
?
-
-
the clostridial neurotoxins differ from other proteases in the recognition of the tertiary structure of the target rather than the sequence of the peptide bond to be cleaved
-
-
?
additional information
?
-
-
no hydrolysis of short peptides spanning the respective cleavage sites of the target proteins
-
-
?
additional information
?
-
-
the heavy chain mediates the binding of the toxin with ganglioside and glycoprotein receptors at the neuronal surface, followed by toxin entry by means of receptor-mediated endocytosis. It mediates the translocation of the light chain into the neuronal cytosol, where it functions as a Zn2+-dependent endoprotease
-
-
?
additional information
?
-
-
development and evaluation of in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors, development of FRET substrates, overview
-
-
?
additional information
?
-
-
no hydrolysis of short peptides spanning the respective cleavage sites of the target proteins
-
-
?
additional information
?
-
-
the botulinum neurotoxins are divided into two groups: the A-E type and the B-D-F-tetanus toxin type
-
-
?
additional information
?
-
-
N-ethylmaleimide sensitive factor (i.e. NSF), alpha/beta-SNAP or gamma-SNAP
-
-
?
additional information
?
-
-
the botulinum neurotoxins are divided into two groups: the A-E type and the B-D-F-tetanus toxin type
-
-
?
additional information
?
-
-
N-ethylmaleimide sensitive factor (i.e. NSF), alpha/beta-SNAP or gamma-SNAP
-
-
?
additional information
?
-
-
clostridial neurotoxins are the causative agents of the neuroparalytic diseases botulism and tetanus blocking neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors, SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery
-
-
?
additional information
?
-
-
the catalytic component of the clostridial neurotoxins is their light chain, a Zn2+ endopeptidase, cleavage site specificity, overview
-
-
?
additional information
?
-
-
mapping experiment shows that residues 40-87 of vesicle-associated membrane protein 2 are sufficient for efficient TeNT cleavage. Mutations in vesicle-associated membrane protein 2 for analysation of binding kinetics to TeNT
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