Structure and mechanism of spermidine synthases.
Aminopropyltransferases transfer aminopropyl groups from decarboxylated S-adenosylmethionine to amine acceptors, forming polyamines. Structural and biochemical studies have been carried out with the human spermidine synthase, which is highly specific for putrescine as the amine acceptor, and the Thermotoga maritima spermidine synthase, which prefers putrescine but is more tolerant of other substrates. Comparison of the structures of the human spermidine synthase with both substrates and products with the known structure of T. maritima spermidine synthase complexed to a multisubstrate analogue inhibitor and analysis of the properties of site-directed mutants provide a general mechanistic hypothesis for the aminopropyl transfer reaction. The studies also provide a structural basis for the specificity of the spermidine synthase subclass of the aminopropyltransferase family.
Wu
Hong
H
Structural Genomics Consortium, University of Toronto, 100 College Street, Toronto, Ontario, M5G 1L5, Canada.
Min
Jinrong
J
Ikeguchi
Yoshihiko
Y
Zeng
Hong
H
Dong
Aiping
A
Loppnau
Peter
P
Pegg
Anthony E
AE
Plotnikov
Alexander N
AN
D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011700:Putrescine / Q000737:chemistry; D011436:Spermidine Synthase / Q000737:chemistry* / Q000235:genetics; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000201:enzymology
D011436:Spermidine Synthase; D011700:Putrescine