Yang Meng-Yin, Morrow Janet R, Richard John P
Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260, USA.
Bioorg Chem. 2007 Oct;35(5):366-74. doi: 10.1016/j.bioorg.2007.02.003. Epub 2007 Apr 16.
The values of K(i) for methylphosphate dianion (MP(2-)) inhibition of the cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) catalyzed by 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(1)(H(2)O)) approach a small limiting value of 6 microM at pH<pK(a)=7.8 for deprotonation of the catalyst to form Zn(2)(1)(HO(-)). There is a 1600-fold difference in the affinity of a phosphate diester monoanion (diethylphosphate) and phosphate monester dianion (MP(2-)) for Zn(2)(1)(H(2)O). This suggests that the latter is an analog for the transition state dianion for the cleavage reaction of HpPNP and other phosphate diesters. The observation that this transition state analog binds selectively to Zn(2)(1)(H(2)O) provides strong evidence that this is the active form of the catalyst which binds selectively to the ionized substrate. The efficiency of catalysis of the cleavage of phosphate diesters by Zn(2)(1)(H(2)O) and proteins is compared.
在pH < pK(a)=7.8（催化剂去质子化形成Zn(2)(1)(HO(-))）时，甲基磷酸二价阴离子（MP(2-)）对1,3-双(1,4,7-三氮杂环壬-1-基)-2-羟基丙烷（Zn(2)(1)(H(2)O)）催化2-羟丙基-4-硝基苯基磷酸酯（HpPNP）裂解的抑制作用的K(i)值接近6 microM的小极限值。磷酸二酯单阴离子（磷酸二乙酯）和磷酸单酯二价阴离子（MP(2-)）对Zn(2)(1)(H(2)O)的亲和力相差1600倍。这表明后者是HpPNP和其他磷酸二酯裂解反应过渡态二价阴离子的类似物。这种过渡态类似物选择性结合到Zn(2)(1)(H(2)O)的观察结果提供了有力证据，表明这是选择性结合离子化底物的催化剂活性形式。比较了Zn(2)(1)(H(2)O)和蛋白质催化磷酸二酯裂解的效率。
