Ikeguchi Yoshihiko, Bewley Maria C, Pegg Anthony E
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295.
J Biochem. 2006 Jan;139(1):1-9. doi: 10.1093/jb/mvj019.
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.
氨基丙基转移酶利用脱羧的S-腺苷甲硫氨酸作为氨基丙基供体和胺受体来形成多胺。本综述涵盖了它们的结构、作用机制、抑制、调节和功能。最著名的氨基丙基转移酶是亚精胺合酶和精胺合酶，但该家族的其他成员包括N(1)-氨基丙基胍丁胺合酶也已得到表征。亚精胺合酶是真核生物中的一个必需基因，分布非常广泛。通过对来自嗜热栖热菌的与多底物类似物抑制剂S-腺苷-1,8-二氨基-3-硫代辛烷结合的亚精胺合酶进行结构研究，确定了活性位点中高度保守的关键区域。基于这些研究，可以提出氨基丙基转移酶催化的一般机制。精胺合酶分布较不广泛，对酵母生长不是必需的。然而，缺乏精胺合酶的Gy小鼠有多种症状，包括严重的生长迟缓、不育、耳聋、神经异常和猝死倾向，而通过精胺合酶的转基因表达可以预防所有这些症状。由于剪接位点变异导致人类男性精胺合酶大幅减少会引起伴有智力迟钝、肌张力减退和骨骼异常的斯奈德-罗宾逊综合征。
