spermidine synthase | |||||||
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Identifiers | |||||||
Symbol | SRM | ||||||
Alt. symbols | SRML1 | ||||||
NCBI gene | 6723 | ||||||
HGNC | 11296 | ||||||
OMIM | 182891 | ||||||
RefSeq | NM_003132 | ||||||
UniProt | P19623 | ||||||
Other data | |||||||
EC number | 2.5.1.16 | ||||||
Locus | Chr. 1 p36-p22 | ||||||
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Spermidine synthase is an enzyme (EC 2.5.1.16) that catalyzes the transfer of the propylamine group from S-adenosylmethioninamine to putrescine in the biosynthesis of spermidine. The systematic name is S-adenosyl 3-(methylthio)propylamine:putrescine 3-aminopropyltransferase and it belongs to the group of aminopropyl transferases. It does not need any cofactors. Most spermidine synthases exist in solution as dimers.[1]
With exception of the spermidine synthases from Thermotoga maritimum and from Escherichia coli, which accept different kinds of polyamines, all enzymes are highly specific for putrescine.[2] No known spermidine synthase can use S-adenosyl methionine. This is prevented by a conserved aspartatyl residue in the active site, which is thought to repel the carboxyl moiety of S-adenosyl methionine.[3] The putrescine-N-methyl transferase whose substrates are putrescine and S-adenosyl methionine, and which is evolutionary related to the spermidine synthases, lacks this aspartyl residue.[4] It is even possible to convert the spermidine synthase by some mutations to a functional putrescine-N-methyltransferase.[5]
It is assumed that the synthesis of spermidine follows the Sn2 mechanism.[6] There is some uncertainty if the reaction occurs via a ping-pong or via a ternary-complex mechanism. Some kinetic data, but not all, suggest a ping-pong mechanism,[7] while the investigation of the stereochemical path of the reaction argues for a ternary-complex mechanism.[8] Prior to the nucleophilic attack of the putrescine onto the S-adenosylmethioninamine the putrescine has to be deprotonated rendering the nitrogen nucleophilic since the putrescine is protonated at physiological pH and is therefore inactive.
The spermidine synthase can be inhibited by a wide variety of analogues of putrescine, S-adenosyl methioninamine and transition state analogues as Adodato (for further information see here)