Structural basis for activation of cobalt-carbon bond and control of adenosyl radical in coenzyme B12 catalysis
Structural basis for activation of cobalt-carbon bond and control of adenosyl radical in coenzyme B12 catalysis
复制标题
辅酶B12催化中钴碳键活化和腺苷自由基控制的结构基础
作者：
Shibata;N.;Toraya;T.
腺苷钴胺素（Adenosylcobalamin，简写为AdenosylCbl）或辅酶B12，是一种天然存在的有机金属化合物，作为酶的辅因子，催化从细菌到动物的各种生物体中的分子内基团转移反应和核糖核苷酸还原。辅酶Cbl依赖性酶是自由基酶，其通过辅酶的钴-碳（Co-C）键的均裂产生腺苷自由基用于催化。这些酶如何激活并裂解Co-C键以形成腺苷自由基？酶如何利用腺苷自由基的高反应活性来抑制不良副反应？我们最近的结构研究旨在解决二醇脱氢酶和乙醇胺氨裂解酶的这些问题，确定了Co-C键的空间应变和腺苷自由基的构象稳定对辅酶B12催化的至关重要性。我们在这里概述我们的结果与这些消除异构酶，并与其他自由基B12酶获得的结果进行比较。
Adenosylcobalamin (AdoCbl), or coenzyme B12, is a naturally occurring organometallic compound that serves as a cofactor for enzymes that catalyze intramolecular group‐transfer reactions and ribonucleotide reduction in a wide variety of organisms from bacteria to animals. AdoCbl‐dependent enzymes are radical enzymes that generate an adenosyl radical by homolysis of the coenzyme's cobalt‐carbon (Co−C) bond for catalysis. How do the enzymes activate and cleave the Co−C bond to form the adenosyl radical? How do the enzymes utilize the high reactivity of the adenosyl radical for catalysis by suppressing undesirable side reactions? Our recent structural studies, which aimed to solve these problems with diol dehydratase and ethanolamine ammonia‐lyase, established the crucial importance of the steric strain of the Co−C bond and conformational stabilization of the adenosyl radical for coenzyme B12catalysis. We outline here our results obtained with these eliminating isomerases and compare them with those obtained with other radical B12enzymes.