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Literature summary for 2.5.1.16 extracted from

  • 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 (2011), Protein Sci., 20, 1836-1844.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression of the His-tagged enzyme in Escherichia coli strain BL21(DE3) Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
decarboxylated S-adenosylhomocysteine active site binding structure, overview Homo sapiens
decarboxylated S-adenosylhomocysteine
-
Plasmodium falciparum
decarboxylated S-adenosylhomocysteine
-
Thermotoga maritima

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-adenosylmethioninamine + putrescine Plasmodium falciparum
-
S-methyl-5'-thioadenosine + spermidine
-
?
S-adenosylmethioninamine + putrescine Thermotoga maritima
-
S-methyl-5'-thioadenosine + spermidine
-
?
S-adenosylmethioninamine + putrescine Homo sapiens
-
S-methyl-5'-thioadenosine + spermidine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P19623
-
-
Plasmodium falciparum
-
-
-
Thermotoga maritima
-
-
-

Reaction

Reaction Comment Organism Reaction ID
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 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
S-adenosylmethioninamine + putrescine
-
Plasmodium falciparum S-methyl-5'-thioadenosine + spermidine
-
?
S-adenosylmethioninamine + putrescine
-
Thermotoga maritima S-methyl-5'-thioadenosine + spermidine
-
?
S-adenosylmethioninamine + putrescine
-
Homo sapiens S-methyl-5'-thioadenosine + spermidine
-
?

Synonyms

Synonyms Comment Organism
SPDS
-
Plasmodium falciparum
SPDS
-
Thermotoga maritima
SPDS
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Plasmodium falciparum
25
-
assay at Thermotoga maritima
25
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Plasmodium falciparum
8
-
assay at Thermotoga maritima
8
-
assay at Homo sapiens