Woggon W D, Wagenknecht H A, Claude C
Institute of Organic Chemistry, University of Basel, Switzerland.
J Inorg Biochem. 2001 Feb;83(4):289-300. doi: 10.1016/s0162-0134(00)00175-6.
In view of recent results from different sources, the reaction mechanisms of two heme-thiolate proteins, cytochrome P450cam and chloroperoxidase (CPO), are discussed. In this context a mechanism of CPO is proposed which includes H2O2 cleavage, subsequent formation of compound I and the identification of two elusive intermediates. The HOCl adduct of the iron(III)porpyhrin is the catalytically competent Cl+ donor chlorinating activated C-H bonds of substrates bound to the enzyme. Pulse-EPR characterization of an enzyme model of the resting state of P450cam suggests a role of the electric field of the protein for stabilizing the low-spin state of the cofactor of the enzyme. It is further suggested that the same effect of the protein may trigger the reactivity of compound I such that both concerted and two-step reactions are feasible within the concept of a Two-State-Reactivity. This review emphasizes the value of synthetic enzyme models complementing investigations of the native proteins.
鉴于来自不同来源的近期研究结果，本文讨论了两种血红素硫醇盐蛋白，即细胞色素P450cam和氯过氧化物酶（CPO）的反应机制。在此背景下，提出了一种CPO的机制，其中包括H2O2裂解、随后化合物I的形成以及两种难以捉摸的中间体的鉴定。铁（III）卟啉的HOCl加合物是具有催化活性的Cl+供体，可氯化与酶结合的底物的活化C-H键。对P450cam静止状态的酶模型进行的脉冲EPR表征表明，蛋白质的电场在稳定酶辅因子的低自旋状态方面发挥了作用。进一步表明，蛋白质的相同作用可能会触发化合物I的反应活性，从而使得在双态反应性概念内，协同反应和两步反应都是可行的。本综述强调了合成酶模型对天然蛋白质研究的补充价值。
