spermidine synthase | |
Caption: | Spermidine synthase tetramer, Bacillus subtilis |
Width: | 270 |
Hgncid: | 11296 |
Symbol: | SRM |
Altsymbols: | SRML1 |
Entrezgene: | 6723 |
Omim: | 182891 |
Refseq: | NM_003132 |
Uniprot: | P19623 |
Ecnumber: | 2.5.1.16 |
Chromosome: | 1 |
Arm: | p |
Band: | 36 |
Locussupplementarydata: | -p22 |
Spermidine synthase is an enzyme 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)