Wilson D K, Quiocho F A
Howard Hughes Medical Institute, Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA.
Nat Struct Biol. 1994 Oct;1(10):691-4. doi: 10.1038/nsb1094-691.
Formation of tetrahedral transition intermediates is a key step in many enzyme catalyzed reactions. Much of our understanding of these and other intermediates, at the atomic level, has come from crystallographic studies of very few enzymes with bound, synthetic, transition-state analogues. Here we present the structure of adenosine deaminase, a zinc-metalloenzyme critical in both purine metabolism and development of the lymphoid system, having performed a stereospecific hydroxide addition to the C6 of inosine. This addition causes the O6 oxygen of inosine to assume an orientation analogous to the position of the amino leaving group of the tetrahedral intermediate in the enzyme-catalyzed hydrolytic deamination of adenosine to inosine.
四面体过渡中间体的形成是许多酶催化反应中的关键步骤。我们在原子水平上对这些及其他中间体的许多理解，来自于对极少数结合了合成过渡态类似物的酶的晶体学研究。在此，我们展示了腺苷脱氨酶的结构，这是一种锌金属酶，在嘌呤代谢和淋巴系统发育中都至关重要，它对肌苷的C6进行了立体特异性的氢氧化物加成。这种加成使肌苷的O6氧呈现出一种类似于腺苷酶催化水解脱氨生成肌苷过程中四面体中间体氨基离去基团位置的取向。
