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Structures	Swiss-model
Domains	InterPro

spermidine synthase
spermidine synthase
	Spermidine synthase tetramer, Bacillus subtilis
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
Structures
Search for
Structures	Swiss-model
Domains	InterPro

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]

Specificity

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]

Mechanism

It is assumed that the synthesis of spermidine follows the S_n2 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.

Inhibitors

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)

References

^ Ikeguchi Y, Bewley MC, Pegg AE (January 2006). "Aminopropyltransferases: function, structure and genetics". Journal of Biochemistry. 139 (1): 1–9. doi:10.1093/jb/mvj019. PMID 16428313.
^ Wu H, Min J, Ikeguchi Y, Zeng H, Dong A, Loppnau P, Pegg AE, Plotnikov AN (July 2007). "Structure and mechanism of spermidine synthases". Biochemistry. 46 (28): 8331–9. doi:10.1021/bi602498k. PMID 17585781.
^ Korolev S, Ikeguchi Y, Skarina T, Beasley S, Arrowsmith C, Edwards A, Joachimiak A, Pegg AE, Savchenko A (January 2002). "The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor". Nature Structural Biology. 9 (1): 27–31. doi:10.1038/nsb737. PMC 2792006. PMID 11731804.
^ Biastoff S, Brandt W, Dräger B (2009-10-01). "Putrescine N-methyltransferase--the start for alkaloids". Phytochemistry. Evolution of Metabolic Diversity. 70 (15–16): 1708–18. Bibcode:2009PChem..70.1708B. doi:10.1016/j.phytochem.2009.06.012. PMID 19651420.
^ Junker A, Fischer J, Sichhart Y, Brandt W, Dräger B (2013-01-01). "Evolution of the key alkaloid enzyme putrescine N-methyltransferase from spermidine synthase". Frontiers in Plant Science. 4: 260. doi:10.3389/fpls.2013.00260. PMC 3725402. PMID 23908659.
^ Golding B, Nassereddin lK, Billington D. "The Biosynthesis of Spermidine. Part I : Biosynthesis of Spermidine from L-[3,4-13C2] Methionine and L-[2,3,3-2H3] Methionine". J. Chem. Soc. Perkin Trans.
^ Yoon SO, Lee YS, Lee SH, Cho YD (June 2000). "Polyamine synthesis in plants: isolation and characterization of spermidine synthase from soybean (Glycine max) axes". Biochimica et Biophysica Acta (BBA) - General Subjects. 1475 (1): 17–26. doi:10.1016/s0304-4165(00)00039-8. PMID 10806333.
^ Golding B, Nassereddin I (1985). "The Biosynthesis of Spermidine. Part 3: The Stereochemistry of the Formationof the N-CH2, Group in the Biosynthesis of Spermidine". J. Chem. Soc. Perkin Trans.: 2017. doi:10.1039/P19850002017.