spermidine synthase

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.{{cite journal | vauthors = Wu H, Min J, Ikeguchi Y, Zeng H, Dong A, Loppnau P, Pegg AE, Plotnikov AN | title = Structure and mechanism of spermidine synthases | journal = Biochemistry | volume = 46 | issue = 28 | pages = 8331–9 | date = July 2007 | pmid = 17585781 | doi = 10.1021/bi602498k | url = https://figshare.com/articles/journal_contribution/2996425 }} 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.{{cite journal | vauthors = Korolev S, Ikeguchi Y, Skarina T, Beasley S, Arrowsmith C, Edwards A, Joachimiak A, Pegg AE, Savchenko A | title = The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor | journal = Nature Structural Biology | volume = 9 | issue = 1 | pages = 27–31 | date = January 2002 | pmid = 11731804 | doi = 10.1038/nsb737 | pmc=2792006}} 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.{{cite journal | vauthors = Biastoff S, Brandt W, Dräger B | title = Putrescine N-methyltransferase--the start for alkaloids | journal = Phytochemistry | volume = 70 | issue = 15–16 | pages = 1708–18 | date = 2009-10-01 | pmid = 19651420 | doi = 10.1016/j.phytochem.2009.06.012 | series = Evolution of Metabolic Diversity | bibcode = 2009PChem..70.1708B }} It is even possible to convert the spermidine synthase by some mutations to a functional putrescine-N-methyltransferase.{{cite journal | vauthors = Junker A, Fischer J, Sichhart Y, Brandt W, Dräger B | title = Evolution of the key alkaloid enzyme putrescine N-methyltransferase from spermidine synthase | journal = Frontiers in Plant Science | volume = 4 | pages = 260 | date = 2013-01-01 | pmid = 23908659 | doi = 10.3389/fpls.2013.00260 | pmc=3725402| doi-access = free }}

It is assumed that the synthesis of spermidine follows the S_n2 mechanism.{{cite journal | first1 = B.T. | last1 = Golding | first2 = l. K. | last2 = Nassereddin| first3 = D.C. | last3 = Billington | name-list-style = vanc | title = The Biosynthesis of Spermidine. Part I : Biosynthesis of Spermidine from L-[3,4-13C2] Methionine and L-[2,3,3-2H3] Methionine | journal = J. Chem. Soc. Perkin Trans. }} 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,{{cite journal | vauthors = Yoon SO, Lee YS, Lee SH, Cho YD | title = Polyamine synthesis in plants: isolation and characterization of spermidine synthase from soybean (Glycine max) axes | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1475 | issue = 1 | pages = 17–26 | date = June 2000 | pmid = 10806333 | doi=10.1016/s0304-4165(00)00039-8}} while the investigation of the stereochemical path of the reaction argues for a ternary-complex mechanism.{{cite journal | first1 = B.T. | last1 = Golding | first2 = I.K. | last2 = Nassereddin | name-list-style = vanc | title = The Biosynthesis of Spermidine. Part 3: The Stereochemistry of the Formationof the N-CH2, Group in the Biosynthesis of Spermidine | journal = J. Chem. Soc. Perkin Trans. | doi = 10.1039/P19850002017 | pages=2017| year = 1985 }} 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 [http://www.brenda-enzymes.org/enzyme.php?ecno=2.5.1.16#INHIBITORS here])

• Spermine synthase
• Adenosylmethionine decarboxylase

{{Reflist|33em}}

{{Commonscat}}

• [http://www.brenda-enzymes.org/enzyme.php?ecno=2.5.1.16 Spermidine synthase] at BRENDA
• [http://enzyme.expasy.org/EC/2.5.1.16 Spermidine synthase] at ExPASy
• {{MeshName|Spermidine+synthase}}

{{Alkyl and aryl transferases}}

{{Enzymes}}

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Category:EC 2.5.1

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