HOW A PROTEIN BINDS B-12 - A 3.0-ANGSTROM X-RAY STRUCTURE OF B-12-BINDING DOMAINS OF METHIONINE SYNTHASE
HOW A PROTEIN BINDS B-12 - A 3.0-ANGSTROM X-RAY STRUCTURE OF B-12-BINDING DOMAINS OF METHIONINE SYNTHASE
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DOI：
10.1126/science.7992050
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发表时间：
1994-12-09
期刊：
影响因子：
56.9
通讯作者：
LUDWIG, ML
中科院分区：
文献类型：
--
作者：
DRENNAN, CL;HUANG, S;LUDWIG, ML
在3.0埃分辨率下测定了来自大肠杆菌的含27千道尔顿甲基钴胺素合酶片段的晶体结构。该结构描述钴胺素-蛋白质相互作用，并揭示咕啉大环位于螺旋氨基末端结构域和α/β羧基末端结构域之间，该结构域是Rossmann折叠的变体。甲钴胺在结合蛋白质时发生构象变化;与游离辅因子中的钴配位的二甲基苯并咪唑基团远离咕啉，并被蛋白质提供的组氨酸取代。序列Asp-X-His-X-X-Gly，其中包含这个组氨酸配体，是保守的腺苷钴胺素依赖性酶甲基丙二酰辅酶A β和谷氨酸酯β，这表明二甲基苯并咪唑的位移将是一个共同的功能，许多钴胺素结合蛋白。因此，钴配体His（759）和相邻残基Asp（757）和Ser（810）可形成催化四联体Co-His-Asp-Ser，其调节甲硫氨酸合酶中B-12辅基的反应性。
The crystal structure of a 27-kilodalton methylcobalamin-containing fragment of methi onine synthase from Escherichia coli was determined at 3.0 Angstrom resolution. This structure depicts cobalamin-protein interactions and reveals that the corrin macrocycle lies between a helical amino-terminal domain and an alpha/beta carboxyl-terminal domain that is a variant of the Rossmann fold. Methylcobalamin undergoes a conformational change on binding the protein; the dimethylbenzimidazole group, which is coordinated to the cobalt in the free cofactor, moves away from the corrin and is replaced by a histidine contributed by the protein. The sequence Asp-X-His-X-X-Gly, which contains this histidine ligand, is conserved in the adenosylcobalamin-dependent enzymes methylmalonyl-coenzyme A mutase and glutamate mutase, suggesting that displacement of the dimethylbenzimidazole will be a feature common to many cobalamin-binding proteins. Thus the cobalt ligand, His(759), and the neighboring residues Asp(757) and Ser(810), may form a catalytic quartet, Co-His-Asp-Ser, that modulates the reactivity of the B-12 prosthetic group in methionine synthase.