title: Aminopropyltransferases: function, structure and genetics.
abstract: Aminopropyltransferases use decarboxylated S-adenosylmethionine as an aminopropyl donor and an amine acceptor to form polyamines. This review covers their structure, mechanism of action, inhibition, regulation and function. The best known aminopropyltransferases are spermidine synthase and spermine synthase but other members of this family including an N(1)-aminopropylagmatine synthase have been characterized. Spermidine synthase is an essential gene in eukaryotes and is very widely distributed. Key regions in the active site, which are very highly conserved, were identified by structural studies with spermidine synthase from Thermotoga maritima bound to S-adenosyl-1,8-diamino-3-thiooctane, a multisubstrate analog inhibitor. A general mechanism for catalysis by aminopropyltransferases can be proposed based on these studies. Spermine synthase is less widely distributed and is not essential for growth in yeast. However, Gy mice lacking spermine synthase have multiple symptoms including a profound growth retardation, sterility, deafness, neurological abnormalities and a propensity to sudden death, which can all be prevented by transgenic expression of spermine synthase. A large reduction in spermine synthase in human males due to a splice site variant causes Snyder-Robinson syndrome with mental retardation, hypotonia and skeletal abnormalities.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ikeguchi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bewley
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pegg
mesh_terms: D000588:Amines / Q000378:metabolism; D008958:Models, Molecular; D030821:Plants, Genetically Modified; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000201:enzymology
chemical_list: D000588:Amines; D011436:Spermidine Synthase