View source for Spermidine synthase

{{Short description|Class of enzymes}}
{{infobox protein
|Name=spermidine synthase
|caption=Spermidine synthase tetramer, Bacillus subtilis
|image=1iy9.jpg
|width=270
|HGNCid=11296
|Symbol=SRM
|AltSymbols=SRML1
|EntrezGene=6723
|OMIM=182891
|RefSeq=NM_003132
|UniProt=P19623
|PDB=
|ECnumber=2.5.1.16
|Chromosome=1
|Arm=p
|Band=36
|LocusSupplementaryData=-p22
}}
'''Spermidine synthase''' is an [[enzyme]] ({{EC number|2.5.1.16}}) that [[transferase|catalyzes the transfer]] of the propylamine group from [[S-Adenosylmethioninamine|''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.<ref>{{cite journal | vauthors = Ikeguchi Y, Bewley MC, Pegg AE | title = Aminopropyltransferases: function, structure and genetics | journal = Journal of Biochemistry | volume = 139 | issue = 1 | pages = 1–9 | date = January 2006 | pmid = 16428313 | doi = 10.1093/jb/mvj019 }}</ref>

== 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.<ref>{{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 | url-access = subscription }}</ref> No known spermidine synthase can use [[S-Adenosyl methionine|''S''-adenosyl methionine]]. This is prevented by a conserved [[Aspartic acid|aspartatyl residue]] in the active site, which is thought to repel the carboxyl moiety of ''S''-adenosyl methionine.<ref>{{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}}</ref> The [[Putrescine N-methyltransferase|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.<ref>{{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 }}</ref> It is even possible to convert the spermidine synthase by some mutations to a functional putrescine-N-methyltransferase.<ref>{{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 }}</ref>

== Mechanism ==
It is assumed that the synthesis of spermidine follows the [[SN2 reaction|S<sub>n</sub>2 mechanism]].<ref>{{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. }}</ref> There is some uncertainty if the reaction occurs via a [[Ping-pong mechanism|ping-pong]] or via a [[Enzyme kinetics|ternary-complex mechanism]]. Some kinetic data, but not all, suggest a ping-pong mechanism,<ref>{{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}}</ref> while the investigation of the stereochemical path of the reaction argues for a ternary-complex mechanism.<ref>{{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 }}</ref> 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 [http://www.brenda-enzymes.org/enzyme.php?ecno=2.5.1.16#INHIBITORS here])

== See also ==
* [[Spermine synthase]]
* [[Adenosylmethionine decarboxylase]]

== References ==
{{Reflist|33em}}

==External links==
{{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]]


{{2.5-enzyme-stub}}