Wu Y Q, Woster P M
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
Biochem Pharmacol. 1995 Apr 18;49(8):1125-33. doi: 10.1016/0006-2952(95)98510-g.
The S-adenosylmethionine (AdoMet) analogue AdoMac [S-(5'-deoxy-5'-adenosyl)-1-ammonio-4-methylsulfonio-2-cyclopen ten e], an enzyme-activated, irreversible inhibitor of the Escherchia coli form of S-adenosylmethionine decarboxylase (AdoMet-DC), also acts as a potent inhibitor of the human form of the enzyme. This analogue has been resolved recently into its four possible diastereomeric forms, and each pure diastereomer has now been evaluated as an inhibitor of human AdoMet-DC. As was the case for the bacterial enzyme, kinetic analysis revealed that the four pure diastereomeric forms of AdoMac differentially inhibit human S-adenosylmethionine decarboxylase (K(i) values ranging between 11 and 63 microM). Although the human and bacterial forms of the enzyme each discriminated between the four diastereomers of AdoMac, each form appeared to bind optimally to a distinctly different diastereomer of the inhibitor. These data suggest that the active sites of human and bacterial AdoMet-DC are distinctly different, and that it may be possible to design inhibitors that are specific for a given form of the enzyme.
S-腺苷甲硫氨酸（AdoMet）类似物AdoMac [S-(5'-脱氧-5'-腺苷基)-1-铵基-4-甲基硫代-2-环戊烯] 是一种酶激活的、不可逆的大肠杆菌S-腺苷甲硫氨酸脱羧酶（AdoMet-DC）抑制剂，它也是人源该酶的有效抑制剂。这种类似物最近已被拆分为四种可能的非对映体形式，并且现在已对每种纯非对映体作为人源AdoMet-DC抑制剂进行了评估。与细菌酶的情况一样，动力学分析表明，AdoMac的四种纯非对映体形式对人源S-腺苷甲硫氨酸脱羧酶的抑制作用不同（抑制常数K(i)值在11至63微摩尔之间）。尽管该酶的人源和细菌形式都能区分AdoMac的四种非对映体，但每种形式似乎都与抑制剂的一种明显不同的非对映体最佳结合。这些数据表明，人源和细菌AdoMet-DC的活性位点明显不同，并且有可能设计出对特定形式的酶具有特异性的抑制剂。
