Information on EC 2.5.1.22 - spermine synthase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.5.1.22
-
RECOMMENDED NAME
GeneOntology No.
spermine synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl 3-(methylthio)propylamine + spermidine = S-methyl-5'-thioadenosine + spermine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aminopropyl group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
spermine biosynthesis
-
-
superpathway of polyamine biosynthesis II
-
-
polyamine pathway
-
-
Cysteine and methionine metabolism
-
-
Arginine and proline metabolism
-
-
beta-Alanine metabolism
-
-
Glutathione metabolism
-
-
Metabolic pathways
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-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl 3-(methylthio)propylamine:spermidine 3-aminopropyltransferase
The enzyme from mammalia is highly specific for spermidine [2,3]. cf. EC 2.5.1.16 (spermidine synthase) and EC 2.5.1.23 (sym-norspermidine synthase).
CAS REGISTRY NUMBER
COMMENTARY hide
74812-43-4
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Chinese cabbage, var. Pak Choy
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
var. domestica
-
-
Manually annotated by BRENDA team
no activity in Caenorhabditis elegans
-
-
-
Manually annotated by BRENDA team
no activity in Hydra magnipapillata
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
only fungi where spermine synthase is found is the Saccharomycotina class of the Ascomycota
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
H2N(CH2)3NH(CH2)4NH2 + S-adenosyl 3-(methylthio)propylamine
H2N(CH2)3NH(CH2)4NH(CH2)3NH2 + S-methyl-5'-thioadenosine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methioninamine + spermidine
5'-methylthioadenosine + spermine
show the reaction diagram
S-adenosylmethioninamine + 1,8-diaminooctane
5'-methylthioadenosine + N-(3-aminopropyl)octane-1,8-diamine
show the reaction diagram
-
poor substrate
-
-
?
S-adenosylmethioninamine + 6,6-difluorospermidine
5'-methylthioadenosine + 6,6-difluorospermine
show the reaction diagram
-
-
-
-
?
S-adenosylmethioninamine + 6-monofluorospermidine
5'-methylthioadenosine + 6-monofluorospermine
show the reaction diagram
-
-
-
-
?
S-adenosylmethioninamine + 7,7-difluorospermidine
5'-methylthioadenosine + 7,7-difluorospermine
show the reaction diagram
-
-
-
-
?
S-adenosylmethioninamine + 7-monofluorospermidine
5'-methylthioadenosine + 7-monofluorospermine
show the reaction diagram
-
-
-
-
?
S-adenosylmethioninamine + N-(3-aminopropyl)cadaverine
5'-methylthioadenosine + ?
show the reaction diagram
-
poor substrate
-
-
?
S-adenosylmethioninamine + spermidine
5'-methylthioadenosine + spermine
show the reaction diagram
S-adenosylmethioninamine + spermidine
5'-methylthioadenosine + spermine + H+
show the reaction diagram
-
Polyamine sythesis, addition of a second aminopropyl group to the N-10 position of spermidine. The active site with a bound spermidine molecule contains an Asp276 residue, which is in an ideal position to facilitate the deprotonation of the N-10 amino group of spermidine that attacks the C-atom of the aminopropyl group of decarboxylated S-adenosylmethionine
-
-
?
S-adenosylmethioninamine + spermidine
S-methyl-5'-thioadenosine + spermine
show the reaction diagram
S-adenosylmethioninamine + sym-homospermidine
5'-methylthioadenosine + ?
show the reaction diagram
-
17% of the activity with spemidine
-
-
?
S-adenosylmethioninamine + sym-norspermidine
5'-methylthioadenosine + ?
show the reaction diagram
-
poor substrate
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosylmethioninamine + spermidine
5'-methylthioadenosine + spermine
show the reaction diagram
S-adenosylmethioninamine + spermidine
5'-methylthioadenosine + spermine + H+
show the reaction diagram
-
Polyamine sythesis, addition of a second aminopropyl group to the N-10 position of spermidine. The active site with a bound spermidine molecule contains an Asp276 residue, which is in an ideal position to facilitate the deprotonation of the N-10 amino group of spermidine that attacks the C-atom of the aminopropyl group of decarboxylated S-adenosylmethionine
-
-
?
S-adenosylmethioninamine + spermidine
S-methyl-5'-thioadenosine + spermine
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3-Diaminopropane
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-
1,8-diaminooctane
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-
1,9-diamino-4-azanonane
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weak
1,9-Diamino-5-azanonane
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weak
1-aminooxy-3-N-(3-aminopropyl)-aminopropane
-
competitive inhibitor
1-aminooxy-3-N-[3-aminopropyl]-aminopropane
-
aminooxy analogue of spermidine, kinetics
3,3'-Diaminodipropylamine
-
weak
3-(RS)-(5'-deoxy-5'-carbaadenos-6'-yl)spermidine
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IC50: 750 nM
5'-ethylthioadenosine
5'-methylthioadenosine
5'-methylthiotubercidin
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strong, in vivo and in vitro, kinetics
5-[5'-deoxy-5'-(C)-4',5'-didehydroadenosyl]-L-ornithine
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i.e. compound A9154C, prostate
7,7-Difluorospermidine
7-Monofluorospermidine
N-(3-aminopropyl)cyclohexylamine
N-butyl-1,3-diaminopropane
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IC50: 0.4 mM
N-ethylmaleimide
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in the absence of sulfhydryl compounds
N-[(2-aminooxyethyl)-1,4-diaminobutane]
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competitive inhibitor
N-[2-aminooxyethyl]-1,4-diaminobutane
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aminooxy analogue of spermidine, kinetics
PCMB
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in the absence of sulfhydryl compounds
putrescine
S-5'-Deoxyadenosyl-(5')-1-methyl-3-(methylthio)propylamine
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S-adenosyl-1,12-diamino-3-thio-9-azadodecane
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IC50: 20 nM
S-Adenosyl-1,8-diamino-3-thiooctane
-
weak, prostate
S-Adenosyl-4-methylthiobutyrate
S-Adenosyl-4-thiobutyrate methylester
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prostate
S-adenosyl-D-methionine
S-adenosyl-L-ethionine
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70-98% inhibition at 1 mm
S-adenosyl-L-homocysteine
S-adenosyl-L-methionine
S-Tubercidinylmethionine
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70-98% inhibition at 1 mm
spermine
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
glycerol
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After culture in embryo-inducing medium with 2% glycerol, expression pattern of the gene in the embryos at different stage are analyzed. The expression level of SPMS is progressively increased with maturation of the embryos.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.458
6,6-difluorospermidine
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-
0.093
6-monofluorospermidine
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-
0.00054
7,7-Difluorospermidine
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-
0.0011
7-Monofluorospermidine
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0.0001 - 0.005
S-adenosylmethioninamine
0.006 - 0.2
spermidine
additional information
additional information
-
ratio of kcat/Km value of wild-type is 40000 for substrate spermidine, and 71000000 for S-adenosyl-L-methioninamine, respectively
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0015 - 32
spermidine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0015
1-aminooxy-3-N-(3-aminopropyl)-aminopropane
0.0003
5'-methylthioadenosine
0.186
N-[(2-aminooxyethyl)-1,4-diaminobutane]
0.0017
putrescine
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-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00075
3-(RS)-(5'-deoxy-5'-carbaadenos-6'-yl)spermidine
Mus musculus
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IC50: 750 nM
0.2
N-(3-aminopropyl)cyclohexylamine
Mus musculus
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IC50: 0.2 mM
0.4
N-butyl-1,3-diaminopropane
Mus musculus
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IC50: 0.4 mM
0.00002
S-adenosyl-1,12-diamino-3-thio-9-azadodecane
Mus musculus
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IC50: 20 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.403
-
-
0.455
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placenta
0.579
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8
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broad
7.5
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assay at
7.5 - 8.1
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-
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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nucellar-derived embryogenic callus of Valencia sweet orange is maintained on callus growth medium composed of basal Murashige and Tucker salts, partially supplemented with glycerol, alpha-difluoromethylornithine or putrescine
Manually annotated by BRENDA team
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primary culture of embryonic fibroblast
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
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from patients with Snyder-Robinson syndrome and non-affected individuals
Manually annotated by BRENDA team
expression in nodule inner cortical cells, vascular bundles, and central tissues. Expression is maximal at early stages of nodule development, while at later stages, the level declines
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
41000
-
predicted
78000
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kidney, pore-gradient electrophoresis
88000 - 90000
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brain, gel filtration, sedimentation equilibrium centrifugation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 39700, calculated
homodimer
-
2 identical subunits, each monomer has 3 domains: a C-terminal domain, which contains the active site, a central domain made up of 4 beta-strands and an N-terminal domain with structural similarity to S-adenosylmethionine decarboxylase. Dimerization occurs mainly through interactions between the N-terminal domains. The structures provide an outline of the active site and a plausible model for catalysis. The active site is similar to those of spermidine synthases but has a larger substrate-binding pocket able to accommodate longer substrates. Asp201 and 276, conserved in aminopropyltransferases, play a key part in the catalytic mechanism. By separate expression of both domains, enzymes are inactive and possess rigid tertiary structure, suggesting that human SpmSyn is a fusion protein.
monomer
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deletions of all or part of the N-terminal domain lead to the protein existing as a monomer as determined by gel filtration analysis and to virtually complete loss of activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
analysis of X-ray crystal structure of the wild-type human SMS in complex with spermidine and 5-methylthioadenosine, PDB ID 3C6K, and folding free energy calculations, dimer structure analysis of wild-type and mutant enzymes, overview
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in complex with 5'-methylthioadenosine and spermidine and with 5'-methylthioadenosine and spermine. Enzyme is a dimer of two identical subunits. Each monomer has three domains, a C-terminal domain, which contains the active site and is similar in structure to spermidine synthase, a central domain made up of four beta-strands, and an N-terminal domain with remarkable structural similarity to S-adenosylmethionine decarboxylase
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Purified SpmSyn is crystallized as ternary complex in the presence of spermidine and 5'-methylthioadenosine or spermidine and 5'-methylthioadenosine using the hanging drop vapor diffusion method. The SpmSyn-5'-methylthioadenosine-spermidine complex is crystallized in 12% polyethylene glycol and 0.1 M MES (pH 6.5). The SpmSyn-5'-methylthioadenosine-spermine complex is crystallized in 18% polyethylene glycol, 0.1 M NaCl, and 0.1 M BisTris (pH 6.5). Crystals are soaked in the corresponding mother liquor supplemented with 20% glycerol as cryoprotectant before freezing in liquid nitrogen.
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
bovine serum albumin stabilizes enzyme in dilute solutions
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0C, in buffer containing 0.3 M NaCl and 1 mM spermidine, at least 6 months
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cell lysate is loaded onto a HiTrap chelating column charged with Ni2+. The enzyme is eluted with an imidazole gradient (50-250 mM) at pH 8.0. The protein is loaded onto a Superdex 200 column equilibrated with 20 mM Tris-HCl and 150 mM NaCl. Thrombin is added to combined fractions containing SpmSyn to remove the His-tag. The protein is further purified to homogeneity by ion-exchange chromatography.
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partial; spermine-Sepharose affinity chromatography
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spermine-Sepharose affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA fragment encoding human enzyme is amplified by PCR and subcloned into the pET28a-LIC vector downstream of the polyhistidine coding region. Enzyme is expressed in the Escherichia coli BL21-Codon Plus(DE3)-RIL strain by the addition of 1 mM isopropyl1-thio-beta-D-galactopyranoside. The N-terminally truncated SpmSyn mutants are generated by PCR and subcloned into the pET28a-LIC vector.
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DNA sequence determination and analysis of gene SPMS, construction of expression vectors for recombinant expression in transgenic plants/mutants of genes ACAULIS5, i.e. ACL5, and SPMS
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enzyme overexpression in transgenic mice under control of a composite CMV-IE enhancer-chicken beta-actin promotor, 4 separate founder CAG/SpmS mice are analysed: enzyme expression in all tissues, mostly highly increased compared to the wild-type mice, overview
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expressed in a yeast mutant deficient in Spm synthase, and in the Arabidopsis dwarf mutant acl5
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expression of human spermine synthase in CAGSMS line 8 mice from a composite CMV-IE enhancer/chicken beta-actin promoter. Transgenic expression of spermine synthase in the Gy mice reverse all of the increases in dcAdoMet content and AdoMetDC
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expression of wild-type and mutant enzymes in HEK cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
gene AtSPMS is inducible by acute salt stress and abscisic acid
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA1-129
-
0.02% activity compared to the wild-type enzyme
DELTA1-145
-
no activity
DELTA1-19
-
0.003% activity compared to the wild-type enzyme
DELTA1-43
-
0.0002% activity compared to the wild-type enzyme
DELTA1-82
-
0.00023% activity compared to the wild-type enzyme
DELTA347-366
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truncation of the protein at position 346 removing the last 20 residues lead to a complete loss of activity
DELTA358-366A
-
smaller truncation of only 9 residues has a smaller effect but still reduced activity by 75%
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine