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EC Tree
IUBMB Comments The enzymes from the plant Glycine max and from mammalia are highly specific for putrescine as the amine acceptor [2,7]. The enzymes from the bacteria Escherichia coli and Thermotoga maritima prefer putrescine but are more tolerant towards other amine acceptors, such as spermidine and cadaverine [5,6]. cf. EC 2.5.1.22 (spermine synthase) and EC 2.5.1.23 (sym-norspermidine synthase).
The taxonomic range for the selected organisms is: Homo sapiens The enzyme appears in selected viruses and cellular organisms
Synonyms
spermidine synthase, aminopropyltransferase, spds2, spdsyn, spd synthase, mdspds1, spermidine synthase 1, pgspd, putrescine aminopropyltransferase, spermidine synthetase,
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aminopropyltransferase
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aminopropyltransferase spermidine synthase
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putrescine aminopropyltransferase
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spermidine synthetase
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synthase, spermidine
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SPDS
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S-adenosyl 3-(methylsulfanyl)propylamine + putrescine = S-methyl-5'-thioadenosine + spermidine
S-adenosyl 3-(methylsulfanyl)propylamine + putrescine = S-methyl-5'-thioadenosine + spermidine
Michaelis-Menten kinetics
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S-adenosyl 3-(methylsulfanyl)propylamine + putrescine = S-methyl-5'-thioadenosine + spermidine
general mechanistic hypothesis for the aminopropyl transfer reaction
S-adenosyl 3-(methylsulfanyl)propylamine + putrescine = S-methyl-5'-thioadenosine + spermidine
this mechanism depends on a conserved Asp (residue 173 in hSpdS) in the active site that interacts with the bound amine substrate to deprotonate the attacking nitrogen atom of the amine. This interaction is reinforced by additional interactions of this nitrogen atom with the hydroxyl group of a conserved Tyr (residue 79 in hSpdS) and a backbone carbonyl group (Ser174 in hSpdS). These interactions allow the attack on the methylene carbon atom of the aminopropyl group attached to the sulfonium center of dcAdoMet. Electron transfer to this sulfur atom completes the reaction forming S-methyl-5'-thioadenosine and the polyamine product. The positively charged sulfonium ion is a critical part of the reaction
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aminopropyl group transfer
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S-adenosyl 3-(methylthio)propylamine:putrescine 3-aminopropyltransferase
The enzymes from the plant Glycine max and from mammalia are highly specific for putrescine as the amine acceptor [2,7]. The enzymes from the bacteria Escherichia coli and Thermotoga maritima prefer putrescine but are more tolerant towards other amine acceptors, such as spermidine and cadaverine [5,6]. cf. EC 2.5.1.22 (spermine synthase) and EC 2.5.1.23 (sym-norspermidine synthase).
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5'-methyl,5'-deoxymethylthioadenosine + putrescine
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low activity
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S-adenosylmethioninamine + putrescine
5'-S-methyl-5'-thioadenosine + spermidine
S-adenosylmethioninamine + putrescine
S-methyl-5'-thioadenosine + spermidine
S-adenosylmethioninamine + putrescine
spermidine + 5'-methylthioadenosine
low activity
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additional information
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S-adenosylmethioninamine + putrescine
5'-S-methyl-5'-thioadenosine + spermidine
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S-adenosylmethioninamine + putrescine
5'-S-methyl-5'-thioadenosine + spermidine
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S-adenosylmethioninamine + putrescine
5'-S-methyl-5'-thioadenosine + spermidine
the enzyme is highly specific for putrescine
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S-adenosylmethioninamine + putrescine
S-methyl-5'-thioadenosine + spermidine
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S-adenosylmethioninamine + putrescine
S-methyl-5'-thioadenosine + spermidine
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additional information
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amine substrate specificity, overview
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additional information
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amine substrate specificity, overview
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S-adenosylmethioninamine + putrescine
5'-S-methyl-5'-thioadenosine + spermidine
S-adenosylmethioninamine + putrescine
S-methyl-5'-thioadenosine + spermidine
S-adenosylmethioninamine + putrescine
5'-S-methyl-5'-thioadenosine + spermidine
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S-adenosylmethioninamine + putrescine
5'-S-methyl-5'-thioadenosine + spermidine
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S-adenosylmethioninamine + putrescine
S-methyl-5'-thioadenosine + spermidine
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S-adenosylmethioninamine + putrescine
S-methyl-5'-thioadenosine + spermidine
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4-methylcyclohexylamine
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5'-methylthioadenosine
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decarboxylated S-adenosylhomocysteine
active site binding structure, overview
S-adenosyl-L-methionine
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above 0.01 mM
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Brain Neoplasms
Effects of dicyclohexylamine sulfate, a spermidine synthase inhibitor, in 9L rat brain tumor cells.
Breast Neoplasms
Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line.
Carcinoma
Antitumor effect of dicyclohexylammonium sulfate, a potent inhibitor of spermidine, synthase.
Carcinoma, Hepatocellular
Dicyclohexylamine effects on HTC cell polyamine content and ornithine decarboxylase activity.
Carcinoma, Hepatocellular
Inhibition of spermidine synthase gene expression by transforming growth factor-beta 1 in hepatoma cells.
Carcinoma, Hepatocellular
Specific depletion of spermidine and spermine in HTC cells treated with inhibitors of aminopropyltransferases.
Chagas Disease
An NMR Biochemical Assay for Fragment-Based Drug Discovery: Evaluation of an Inhibitor Activity on Spermidine Synthase of Trypanosoma cruzi.
Chagas Disease
In silico, in vitro, X-ray crystallography, and integrated strategies for discovering spermidine synthase inhibitors for Chagas disease.
Chagas Disease
Polyamine biosynthetic enzymes as drug targets in parasitic protozoa.
Cysts
Arabidopsis spermidine synthase is targeted by an effector protein of the cyst nematode Heterodera schachtii.
Dehydration
Genome-wide identification of genes involved in polyamine biosynthesis and the role of exogenous polyamines in Malus hupehensis Rehd. under alkaline stress.
Hypersensitivity
Engineering a spermidine biosynthetic pathway in Clostridium thermocellum results in increased resistance to furans and increased ethanol production.
Infections
Arginase Is Essential for Survival of Leishmania donovani Promastigotes but Not Intracellular Amastigotes.
Infections
Spermidine synthase is required for virulence of Leishmania donovani.
Infections
Transcriptomic Analysis of Resistant and Susceptible Responses in a New Model Root-Knot Nematode Infection System Using Solanum torvum and Meloidogyne arenaria.
Leishmaniasis
A leishmaniasis study: Structure-based screening and molecular dynamics mechanistic analysis for discovering potent inhibitors of spermidine synthase.
Leishmaniasis
Polyamine biosynthetic enzymes as drug targets in parasitic protozoa.
Leishmaniasis
Spermidine synthase is required for virulence of Leishmania donovani.
Leishmaniasis
Targeting polyamine metabolism for finding new drugs against leishmaniasis: a review.
Leukemia
2-Mercaptoethylamine, a competitive inhibitor of spermidine synthase in mammalian cells.
Leukemia
Antitumor effect of dicyclohexylammonium sulfate, a potent inhibitor of spermidine synthase against P388 leukemia.
Leukemia
Synthesis of N-chlorosulfonyl dicyclohexylamine as a potent inhibitor for spermidine synthase and its effects on human leukemia Molt4B cells.
Leukemia, Lymphoid
Inhibition by polyamines of methylthiopropylamine-induced ornithine decarboxylase in human lymphoid leukemia Molt 4B cells.
Leukemia, Lymphoid
Methylthiopropylamine, a potent inhibitor of spermidine synthase and its antiproliferative effect on human lymphoid leukemia Molt 4B cells.
Lymphoma, B-Cell
Cancer chemoprevention locks onto a new polyamine metabolic target.
Lymphoma, B-Cell
Chemoprevention of B-cell lymphomas by inhibition of the Myc target spermidine synthase.
Malaria
Binding and Inhibition of Spermidine Synthase from Plasmodium falciparum and Implications for In Vitro Inhibitor Testing.
Malaria
Identification of Plasmodium falciparum spermidine synthase active site binders through structure-based virtual screening.
Malaria
Polyamine biosynthetic enzymes as drug targets in parasitic protozoa.
Malaria
Structural and mechanistic insights into the action of Plasmodium falciparum spermidine synthase.
Malaria
The spermidine synthase of the malaria parasite Plasmodium falciparum: molecular and biochemical characterisation of the polyamine synthesis enzyme.
Nematode Infections
Arabidopsis spermidine synthase is targeted by an effector protein of the cyst nematode Heterodera schachtii.
Neoplasms
Binding and Inhibition of Spermidine Synthase from Plasmodium falciparum and Implications for In Vitro Inhibitor Testing.
Neoplasms
Chain-fluorinated polyamines as tumor markers--IV. Comparison of 2-fluoroputrescine and 2,2-difluoroputrescine as substrates of spermidine synthase in vitro and in vivo.
Neoplasms
Chemoprevention of B-cell lymphomas by inhibition of the Myc target spermidine synthase.
Osteoporosis
Modeling Snyder-Robinson Syndrome in multipotent stromal cells reveals impaired mitochondrial function as a potential cause for deficient osteogenesis.
Potassium Deficiency
Polyamine Metabolism in Scots Pine Embryogenic Cells under Potassium Deficiency.
Trypanosomiasis, African
Polyamine biosynthetic enzymes as drug targets in parasitic protozoa.
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0.08
1,4-diaminobutane
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pH 7.4, 37ºC, spleen
0.02
putrescine
pH 7.5, 37°C, recombinant enzyme
0.007
S-adenosyl-3-methylthio-1-propylamine
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pH 7.4, 37ºC, spleen
0.009
S-adenosylmethioninamine
pH 7.5, 37°C, recombinant enzyme
additional information
additional information
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1.9
putrescine
pH 7.5, 37°C, recombinant enzyme
1.9
S-adenosylmethioninamine
pH 7.5, 37°C, recombinant enzyme
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additional information
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development of a high-throughput assay using homogeneous time-resolved fluorescence based on energy transfer from europium cryptate as a donor to crosslinked allophycocyanin XL665 as an acceptor, involving a competitive immunoassay, overview
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additional information
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pI 5.1, in spleen
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22
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assay at room temperature
37
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assay at
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brenda
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Uniprot
brenda
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brenda
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Uniprot
brenda
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brenda
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brenda
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brenda
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brenda
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brenda
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brenda
additional information
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tissue distribution
brenda
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brenda
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physiological function
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spermidine synthhase is responsible for spermdine synthesis from putrescine, the polyamines putrescine, spermidine and spermine are cationic molecules that are found in all eukaryotic cells and are clearly essential to growth and development
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SPEE_HUMAN
302
0
33825
Swiss-Prot
other Location (Reliability: 2 )
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35000
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2 * 35000, SDS-PAGE
62000
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spleen, pore gradient gel electrophoresis
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dimer
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2 * 35000, SDS-PAGE
dimer
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2 * 35000-40000, recombinant FLAG-tagged enzyme, SDS-PAGE
additional information
structure analysis, comparison to the enzyme from Thermotoga maritima
additional information
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structure analysis, comparison to the enzyme from Thermotoga maritima
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purified recombinant enzyme free or in complex with spermidine, putrescine, 5'-methyl, 5'-deoxymethylthioadenosine, and S-adenosylmethionine, hanging drop vapor diffusion method, 20°C, 10 mg/ml protein solution is mixed with reservoir solution, containing 20-25% PEG 3350, 0.1 M (NH4)2SO4, 0.1 M HEPES-NaOH, pH 7.5, and ligands in a ratio of 1: 5 enzyme-ligand, X-ray diffraction structure determination and analysis at 1.9-2.1 A resolution
spermidine synthase in complex with inhibitor decarboxylated S-adenosylhomocysteine and substrate putrescine, hanging drop vapor diffusion method, mixing of 0.0015 ml of 14 mg/ml protein in 20 mM Tris-HCl, pH 8.0, solution with 0.0015 ml of reservoir solution containing 100 mM Tris-HCl, pH 8.4, 200 mM sodium sulfate, and 20% w/v PEG 3350, 5 mM putrescine and 5 mM decarboxylated S-adenosylhomocysteine, 22°C, X-ray diffraction structure determmination and analysis at 2.0 A resolution
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additional information
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generation of transgenic mice overexpressing the human SpdS, the mice are viable and fertile and tissue SpdS activity is increased up to 9fold. This increased SpdS activity does not result in a dramatic elevation of spermidine or spermine levels but leads to a 1.5 to 2fold reduction in tissue spermine:spermidine ratio in heart, muscle and liver tissues with the highest levels of SpdS activity
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80
2 min, recombinant enzyme, inactivation
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-80ºC, 20% glycerol, rapid loss of activity in pancreas preparations
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-80ºC, 20% glycerol, stable for spleen tissue enzyme during storage and freeze-thawings
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ammonium sulfate fractionation, chromatography on DEAE-Cellulose, affinity chromatography, 8700fold purified
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recombinant FLAG-tagged enzyme from HEK-293 cells by affinity chromatography
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recombinant His-tagged enzyme from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography
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expression of the His-tagged enzyme in Escherichia coli strain BL21 (DE3)
expression of the His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene spdS, overexpression in transgenic C57BL/6J mice
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overexpression of soluble FLAG-tagged enzyme in HEK-293T cell cytoplasm
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Kajander, E.O.; Kauppinen, L.I.; Pajula, R.L.; Karkola, K.; Eloranta, T.O.
Purification and partial characterization of human polyamine synthases
Biochem. J.
259
879-886
1989
Bos taurus, Homo sapiens, Rattus norvegicus
brenda
Enomoto, K.; Nagasaki, T.; Yamauchi, A.; Onoda, J.; Sakai, K.; Yoshida, T.; Maekawa, K.; Kinoshita, Y.; Nishino, I.; Kikuoka, S.; Fukunaga, T.; Kawamoto, K.; Numata, Y.; Takemoto, H.; Nagata, K.
Development of high-throughput spermidine synthase activity assay using homogeneous time-resolved fluorescence
Anal. Biochem.
351
229-240
2006
Homo sapiens
brenda
Wu, H.; Min, J.; Ikeguchi, Y.; Zeng, H.; Dong, A.; Loppnau, P.; Pegg, A.E.; Plotnikov, A.N.
Structure and mechanism of spermidine synthases
Biochemistry
46
8331-8339
2007
Homo sapiens (P19623), Homo sapiens, Thermotoga maritima (Q9WZC2), Thermotoga maritima
brenda
Shi, C.; Welsh, P.A.; Sass-Kuhn, S.; Wang, X.; McCloskey, D.E.; Pegg, A.E.; Feith, D.J.
Characterization of transgenic mice with overexpression of spermidine synthase
Amino Acids
42
495-505
2012
Homo sapiens
brenda
Seckute, J.; McCloskey, D.E.; Thomas, H.J.; Secrist, J.A.; Pegg, A.E.; Ealick, S.E.
Binding and inhibition of human spermidine synthase by decarboxylated S-adenosylhomocysteine
Protein Sci.
20
1836-1844
2011
Plasmodium falciparum, Thermotoga maritima, Homo sapiens (P19623), Homo sapiens
brenda
Transporter Classification Database (TCDB):
2.A.1.86.5