Crystal structure of human E1 enzyme and its complex with a substrate analog reveals the mechanism of its phosphatase/enolase activity
Crystal structure of human E1 enzyme and its complex with a substrate analog reveals the mechanism of its phosphatase/enolase activity
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DOI：
10.1016/j.jmb.2005.01.072
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发表时间：
2005-05-13
影响因子：
5.6
通讯作者：
Rao, ZH
中科院分区：
文献类型：
--
作者：
Wang, H;Pang, H;Rao, ZH
烯醇化酶-磷酸酶E1（MASA）是普遍存在的甲硫氨酸补救途径中的双功能酶，其催化2，3-二酮基-5-甲硫基-1-磷酸戊烷的连续反应，以Mg 2+作为辅因子产生酸还原酮代谢物。在这项研究中，我们已经确定了MASA及其复合物的晶体结构与基板模拟1.7埃分辨率的多波长异常衍射和分子置换技术，分别。结构支持磷酸酶活性的机制，并进一步表明烯醇化的可能机制。我们建立了一个底物结合的模型，详细描述了酶促反应和过渡态的形成，这将提供洞察在同一家族的其他酶的反应机制。(c)2005爱思唯尔有限公司保留所有权利。
Enolase-phosphatase E1 (MASA) is a bifunctional enzyme in the ubiquitous methionine salvage pathway that catalyzes the continuous reactions of 2,3-diketo-5-methylthio-1-phosphopentane to yield the aci-reductone metabolite using Mg2+ as cofactor. In this study, we have determined the crystal structure of MASA and its complex with a substrate analog to 1.7 angstrom resolution by multi-wavelength anomalous diffraction and molecular replacement techniques, respectively. The structures support the proposed mechanism of phosphatase activity and further suggest the probable mechanism of enolization. We establish a model for substrate binding to describe in detail the enzymatic reaction and the formation of the transition state, which will provide insight into the reaction mechanisms of other enzymes in the same family. (c) 2005 Elsevier Ltd. All rights reserved.