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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Insight into the mechanism of biological methanol activation based on the crystal structure of the methanol-cobalamin methyltransferase complex
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Insight into the mechanism of biological methanol activation based on the crystal structure of the methanol-cobalamin methyltransferase complex

机译：基于甲醇-钴胺素甲基转移酶复合物的晶体结构洞察生物甲醇的活化机理

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摘要

Some methanogenic and acetogenic microorganisms have the catalytic capability to cleave heterolytically the C-O bond of methanol. To obtain insight into the elusive enzymatic mechanism of this challenging chemical reaction we have investigated the methanol-activating MtaBC complex from Methanosarcina barkeri composed of the zinc-containing MtaB and the 5-hydroxybenzimidazolylcobamide-carrying MtaC subunits. Here we report the 2.5-angstrom crystal structure of this complex organized as a (MtaBC)(2). heterotetramer. MtaB folds as a TIM barrel and contains a novel zinc-binding motif. Zinc(II) lies at the bottom of a funnel formed at the C-terminal beta-barrel end and ligates to two cysteinyl sulfurs (Cys-220 and Cys-269) and one carboxylate oxygen (Glu-164). MtaC is structurally related to the cobalamin-binding domain of methionine synthase. Its corrinoid cofactor at the top of the Rossmann domain reaches deeply into the funnel of MtaB, defining a region between zinc(II) and the corrinoid cobalt that must be the binding site for methanol. The active site geometry supports a S(N)2 reaction mechanism, in which the C-O bond in methanol is activated by the strong electrophile zinc(II) and cleaved because of an attack of the supernucleophile cob(I)amide. The environment of zinc(II) is characterized by an acidic cluster that increases the charge density on the zinc(II), polarizes methanol, and disfavors deprotonation of the methanol hydroxyl group. Implications of the MtaBC structure for the second step of the reaction, in which the methyl group is transferred to coenzyme M, are discussed.
机译：一些产甲烷和产乙酸微生物具有催化能力，可以杂合地裂解甲醇的C-O键。为了深入了解这一具有挑战性的化学反应的酶促机理，我们研究了来自甲烷化甲烷八叠球菌的甲醇活化MtaBC复合物，该复合物由含锌的MtaB和带有5-羟基苯并咪唑基甲酰胺的MtaC亚基组成。在这里，我们报道了这种复合物的2.5埃晶体结构，其组织为（MtaBC）（2）。异四聚体。 MtaB可折叠为TIM桶，并包含新颖的锌结合基序。锌（II）位于在C端β-桶末端形成的漏斗底部，与两个半胱氨酰硫（Cys-220和Cys-269）和一个羧酸氧（Glu-164）连接。 MtaC在结构上与蛋氨酸合酶的钴胺素结合域有关。它在Rossmann结构域顶部的类corrinoid辅助因子深深地进入MtaB的漏斗，从而定义了锌（II）和类corrinoid钴之间的区域，该区域必须是甲醇的结合位点。活性位点的几何结构支持S（N）2反应机制，其中甲醇中的C-O键被强亲电性锌（II）激活，并由于超亲核性Cob（I）酰胺的攻击而断裂。锌（II）的环境的特征在于酸性簇，该簇增加了锌（II）上的电荷密度，使甲醇极化，并不利于甲醇羟基的去质子化。讨论了MtaBC结构对第二步反应的影响，其中甲基已转移至辅酶M。

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