Nature of the catalytically labile oxygen at the active site of xanthine oxidase
Nature of the catalytically labile oxygen at the active site of xanthine oxidase
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DOI：
10.1021/ja042500o
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发表时间：
2005-03-30
影响因子：
15
通讯作者：
George, GN
中科院分区：
文献类型：
--
作者：
Doonan, CJ;Stockert, A;George, GN
在本文中，我们报告的结果钼K边X-射线吸收研究进行的氧化活性部位的黄嘌呤氧化酶在pH值6和10。这些结果表明，活性中心含有一个末端氧配体（Mo = O）、两个硫醇配体（Mo-S）、一个末端硫基配体（Mo = S）和一个Mo-OH基团。EXAFS分析表明Mo-OH键从pH 6时的1.97埃缩短到pH 10时的1.75埃，这与Mo-O-部分的产生一致。这项研究提供了令人信服的结构证据，在黄嘌呤氧化酶的氧化活性位点的催化氧供体是Mo-OH，而不是Mo-OH 2连接以前建议的X-射线晶体学。这些结果支持的机制引发的碱辅助亲核攻击的基板由Mo-OH。
In this paper we report the results of molybdenum K-edge X-ray absorption studies performed on the oxidized active site of xanthine oxidase at pH 6 and 10. These results indicate that the active site possesses one terminal oxygen ligand (Mo = O), two thiolate ligands (Mo-S), one terminal sulfido ligand (Mo = S), and one Mo-OH moiety. EXAFS analysis demonstrates that the Mo-OH bond shortens from 1.97 angstrom at pH 6 to 1.75 angstrom at pH 10, which is consistent with the generation of a Mo-O- moiety. This study provides convincing structural evidence that the catalytic oxygen donor at the oxidized active site of xanthine oxidase is Mo-OH rather than the Mo-OH2 ligation previously suggested by X-ray crystallography. These results support a mechanism initiated by base-assisted nucleophilic attack of the substrate by Mo-OH.