Seeing the process of histidine phosphorylation in human bisphosphoglycerate mutase
Seeing the process of histidine phosphorylation in human bisphosphoglycerate mutase
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DOI：
10.1074/jbc.m606421200
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发表时间：
2006-12-22
影响因子：
4.8
通讯作者：
Gong, Weimin
中科院分区：
文献类型：
--
作者：
Wang, Yanli;Liu, Lin;Gong, Weimin
双磷酸甘油酸变位酶是一种红细胞特异性酶，催化一系列分子间磷酰基转移反应。其主要功能是合成血红蛋白的变构效应物2,3-二磷酸甘油酸。在本文中，我们直接观察了磷酰基转移过程中酶活性位点和底物的实时运动。解决了人二磷酸甘油酸变位酶与 2,3-二磷酸甘油酸共结晶的一系列高分辨率晶体结构，代表了磷酰基转移反应中的不同时间点。这些结构不仅澄清了有关该酶家族底物结合模式的争论，而且将关键组氨酸磷酸化的整个过程描绘成“慢电影”。据观察，酶构象在反应的不同状态下不断变化。这些结果为“在线”磷酰基转移机制提供了直接证据，并且确定了一些关键残基在磷酰基转移过程中的作用。
Bisphosphoglycerate mutase is an erythrocyte-specific enzyme catalyzing a series of intermolecular phosphoryl group transfer reactions. Its main function is to synthesize 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin. In this paper, we directly observed real-time motion of the enzyme active site and the substrate during phosphoryl transfer. A series of high resolution crystal structures of human bisphosphoglycerate mutase co-crystallized with 2,3-bisphosphoglycerate, representing different time points in the phosphoryl transfer reaction, were solved. These structures not only clarify the argument concerning the substrate binding mode for this enzyme family but also depict the entire process of the key histidine phosphorylation as a "slow movie". It was observed that the enzyme conformation continuously changed during the different states of the reaction. These results provide direct evidence for an "in line" phosphoryl transfer mechanism, and the roles of some key residues in the phosphoryl transfer process are identified.