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Cytochrome P450s:creating novel ligand sets

机译:细胞色素P450:创建新的配体集

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摘要

Cytochromes P450 are a ubiquitous group of hemoproteins that perform vital cellular reactions in all lifeforms.Until recently,it was thought that P450s contained non-covalently bound heme.However,it was established that covalent linkage of the heme macrocycle occurs naturally in one major group of the P450 superfamily.The reaction involves heme linkage to a conserved amino acid and is autocatalytic,occurring as a consequence of P450 turnover.This finding presents opportunities to engineer biotechnologically important P450s to covalently link the heme,in order to stabilize cofactor binding and to enhance operational stability of these P450s.This opportunity has been taken in studies on two important bacterial P450s and has produced variants with intriguingly different properties.In this article we survey the developments in the field,the relationships with heme macrocycle ligations in other proteins and the important impact that recent studies of heme ligation have had on our general appreciation of P450 structure and mechanism.
机译:细胞色素P450是在各种生命形式中都执行重要细胞反应的血红素蛋白的一个普遍存在的组。直到最近,人们认为P450s包含非共价结合的血红素。但是,已经确定血红素大环的共价键自然发生在一个主要的组中。该反应涉及血红素与保守氨基酸的连接,并且是P450周转的结果,它是自催化的。这一发现为工程技术上重要的P450与血红素共价连接提供了机会,从而稳定了辅因子的结合并与之结合。这项机会已被用于研究两个重要的细菌P450,并产生了具有令人惊讶的不同特性的变体。在本文中,我们概述了该领域的发展,与其他蛋白质中血红素大环结扎的关系以及它们之间的关系。最近关于血红素结扎的研究对我们的一般应用有重要影响P450结构和机理的精确化。

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