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Literature summary for 3.4.24.69 extracted from

  • Hakami, R.M.; Ruthel, G.; Stahl, A.M.; Bavari, S.
    Gaining ground: assays for therapeutics against botulinum neurotoxin (2010), Trends Microbiol., 18, 164-172.
    View publication on PubMed
Search for more literature for 3.4.24.69

Activating Compound

Activating Compound Comment Organism Structure
additional information the toxins are synthesized as single polypeptide chains containing both HC and LC that are activated after undergoing posttranslational proteolysis. All BoNT serotypes require the acidification step for inducing muscle failure Clostridium butyricum
additional information the toxins are synthesized as single polypeptide chains containing both HC and LC that are activated after undergoing posttranslational proteolysis. All BoNT serotypes require the acidification step for inducing muscle failure Clostridium botulinum
additional information the toxins are synthesized as single polypeptide chains containing both HC and LC that are activated after undergoing posttranslational proteolysis. All BoNT serotypes require the acidification step for inducing muscle failure Clostridium baratii

Application

Application Comment Organism
additional information development 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, overview Clostridium butyricum
additional information development 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, overview Clostridium botulinum
additional information development 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, overview Clostridium baratii

Inhibitors

Inhibitors Comment Organism Structure
ammonium chloride affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis Clostridium baratii
ammonium chloride affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis Clostridium botulinum
ammonium chloride affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis Clostridium butyricum
bafilomycin A1 inhibits all BoNT serotypes. The ATPase inhibitor also functions as antagonist of the acidification process Clostridium baratii
bafilomycin A1 inhibits all BoNT serotypes. The ATPase inhibitor also functions as antagonist of the acidification process Clostridium botulinum
bafilomycin A1 inhibits all BoNT serotypes. The ATPase inhibitor also functions as antagonist of the acidification process Clostridium butyricum
concanamycin A the ATPase inhibitor also functions as antagonist of the acidification process Clostridium baratii
concanamycin A the ATPase inhibitor also functions as antagonist of the acidification process Clostridium botulinum
concanamycin A the ATPase inhibitor also functions as antagonist of the acidification process Clostridium butyricum
ganglioside GT1b glycoconjugate the synthetic glycoconjugates based on GT1b prevents SNAP-25 cleavage in spinal cord cells of rat embryos Clostridium baratii
ganglioside GT1b glycoconjugate the synthetic glycoconjugates based on GT1b prevents SNAP25 cleavage in spinal cord cells of rat embryos Clostridium botulinum
ganglioside GT1b glycoconjugate the synthetic glycoconjugates based on GT1b prevents SNAP25 cleavage in spinal cord cells of rat embryos Clostridium butyricum
methylamine hydrochloride affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis Clostridium baratii
methylamine hydrochloride affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis Clostridium botulinum
methylamine hydrochloride affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis Clostridium butyricum
additional information evaluation of relevant and available 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. BoNT intoxication steps as targets for inhibitors, schematic overview. Because all BoNT serotypes require the acidification step for inducing muscle failure, developing pan inhibitors that target this stage is an attractive approach. The cell entry of the toxin is inhibited by plant and animal lectines, glycoconjugates, and antibodies. The SNARE cleavage is inhibited by small molecule, peptide, and peptidomimetic inhibitors Clostridium baratii
additional information evaluation of relevant and available 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. BoNT intoxication steps as targets for inhibitors, schematic overview. Because all BoNT serotypes require the acidification step for inducing muscle failure, developing pan inhibitors that target this stage is an attractive approach. The cell entry of the toxin is inhibited by plant and animal lectines, glycoconjugates, and antibodies. The SNARE cleavage is inhibited by small molecule, peptide, and peptidomimetic inhibitors Clostridium botulinum
additional information evaluation of relevant and available 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. BoNT intoxication steps as targets for inhibitors, schematic overview. Because all BoNT serotypes require the acidification step for inducing muscle failure, developing pan inhibitors that target this stage is an attractive approach. The cell entry of the toxin is inhibited by plant and animal lectines, glycoconjugates, and antibodies. The SNARE cleavage is inhibited by small molecule, peptide, and peptidomimetic inhibitors Clostridium butyricum

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ required Clostridium botulinum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Clostridium butyricum 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 Clostridium botulinum 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 Clostridium baratii 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 ?
-
 ?
SNAP-25 + H2O Clostridium butyricum i.e. 25 kDa synaptosome-associated protein ?
-
 ?
SNAP-25 + H2O Clostridium botulinum i.e. 25 kDa synaptosome-associated protein ?
-
 ?
SNAP-25 + H2O Clostridium baratii i.e. 25 kDa synaptosome-associated protein ?
-
 ?
Syntaxin + H2O Clostridium butyricum
-
 ?
-
 ?
Syntaxin + H2O Clostridium botulinum
-
 ?
-
 ?
Syntaxin + H2O Clostridium baratii
-
 ?
-
 ?
VAMP + H2O Clostridium butyricum i.e. neuronal vesicle-associated membrane protein ?
-
 ?
VAMP + H2O Clostridium botulinum i.e. neuronal vesicle-associated membrane protein ?
-
 ?
VAMP + H2O Clostridium baratii i.e. neuronal vesicle-associated membrane protein ?
-
 ?

Organism

Organism UniProt Comment Textmining
Clostridium baratii
-
-
-
Clostridium botulinum
-
 strains from groups I-IV, seven serotypes BoNT/A to BoNT/G
-
Clostridium butyricum
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification the toxins are synthesized as single polypeptide chains containing both heavy chain and light chain that are activated after undergoing posttranslational proteolysis Clostridium butyricum
proteolytic modification the toxins are synthesized as single polypeptide chains containing both heavy chain and light chain that are activated after undergoing posttranslational proteolysis Clostridium botulinum
proteolytic modification the toxins are synthesized as single polypeptide chains containing both heavy chain and light chain that are activated after undergoing posttranslational proteolysis Clostridium baratii

Reaction

Reaction Comment Organism Reaction ID
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 mechanism of action of botulinum neurotoxin Clostridium butyricum
a
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 mechanism of action of botulinum neurotoxin Clostridium baratii
a
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 mechanism of action of botulinum neurotoxin, botulinum toxin binds to a receptor on the neuronal surface, e.g. SV2 receptor for BoNT/A, or synaptotagmin I and II for BoNT/B and BoNT/G, and is subsequently internalized through endocytosis, schematic overview Clostridium botulinum
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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 Clostridium butyricum ?
-
 ?
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 Clostridium botulinum ?
-
 ?
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 Clostridium baratii ?
-
 ?
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 Clostridium butyricum ?
-
 ?
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 Clostridium botulinum ?
-
 ?
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 Clostridium baratii ?
-
 ?
SNAP-25 + H2O i.e. 25 kDa synaptosome-associated protein Clostridium butyricum ?
-
 ?
SNAP-25 + H2O i.e. 25 kDa synaptosome-associated protein Clostridium botulinum ?
-
 ?
SNAP-25 + H2O i.e. 25 kDa synaptosome-associated protein Clostridium baratii ?
-
 ?
SNAP-25 + H2O i.e. 25 kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C Clostridium butyricum ?
-
 ?
SNAP-25 + H2O i.e. 25 kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C Clostridium botulinum ?
-
 ?
SNAP-25 + H2O i.e. 25 kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C Clostridium baratii ?
-
 ?
Syntaxin + H2O
-
 Clostridium butyricum ?
-
 ?
Syntaxin + H2O
-
 Clostridium botulinum ?
-
 ?
Syntaxin + H2O
-
 Clostridium baratii ?
-
 ?
Syntaxin + H2O substrate of BoNT/C Clostridium butyricum ?
-
 ?
Syntaxin + H2O substrate of BoNT/C Clostridium botulinum ?
-
 ?
Syntaxin + H2O substrate of BoNT/C Clostridium baratii ?
-
 ?
VAMP + H2O i.e. neuronal vesicle-associated membrane protein Clostridium butyricum ?
-
 ?
VAMP + H2O i.e. neuronal vesicle-associated membrane protein Clostridium botulinum ?
-
 ?
VAMP + H2O i.e. neuronal vesicle-associated membrane protein Clostridium baratii ?
-
 ?
VAMP + H2O i.e. neuronal vesicle-associated membrane protein, substrate of BoNT/B, /D, /F, and /G Clostridium butyricum ?
-
 ?
VAMP + H2O i.e. neuronal vesicle-associated membrane protein, substrate of BoNT/B, /D, /F, and /G Clostridium botulinum ?
-
 ?
VAMP + H2O i.e. neuronal vesicle-associated membrane protein, substrate of BoNT/B, /D, /F, and /G Clostridium baratii ?
-
 ?

Subunits

Subunits Comment Organism
More each BoNT serotype consists of a heavy chain, HC, of 100 kDa covalently attached by a disulfide bond to a light chain, LC, of 50 kDa Clostridium butyricum
More each BoNT serotype consists of a heavy chain, HC, of 100 kDa covalently attached by a disulfide bond to a light chain, LC, of 50 kDa Clostridium botulinum
More each BoNT serotype consists of a heavy chain, HC, of 100 kDa covalently attached by a disulfide bond to a light chain, LC, of 50 kDa Clostridium baratii

Synonyms

Synonyms Comment Organism
BoNT
-
 Clostridium butyricum
BoNT
-
 Clostridium botulinum
BoNT
-
 Clostridium baratii
Botulinum neurotoxin
-
 Clostridium butyricum
Botulinum neurotoxin
-
 Clostridium botulinum
Botulinum neurotoxin
-
 Clostridium baratii

General Information

General Information Comment Organism
additional information polysialylated ganglioside GT1b can act as a potential receptor for BoNT/A, and synthetic glycoconjugates based on GT1b prevent SNAP25 cleavage in spinal cord cells of rat embryos Clostridium botulinum
physiological function BoNTs inhibit the release of acetylcholine by peripheral cholinergic nerve terminals through a pathway reliant on several distinct stages of action Clostridium butyricum
physiological function BoNTs inhibit the release of acetylcholine by peripheral cholinergic nerve terminals through a pathway reliant on several distinct stages of action Clostridium botulinum
physiological function BoNTs inhibit the release of acetylcholine by peripheral cholinergic nerve terminals through a pathway reliant on several distinct stages of action Clostridium baratii