文章基本信息

标题：Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase
本地全文：下载
作者：John C. Evans ; Donald P. Huddler ; Mark T. Hilgers 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：11
页码：3729-3736
DOI：10.1073/pnas.0308082100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：B12-dependent methionine synthase (MetH) is a large modular enzyme that utilizes the cobalamin cofactor as a methyl donor or acceptor in three separate reactions. Each methyl transfer occurs at a different substrate-binding domain and requires a different arrangement of modules. In the catalytic cycle, the cobalamin-binding domain carries methylcobalamin to the homocysteine (Hcy) domain to form methionine and returns cob(I)alamin to the folate (Fol) domain for remethylation by methyltetrahydrofolate (CH3-H4folate). Here, we describe crystal structures of a fragment of MetH from Thermotoga maritima comprising the domains that bind Hcy and CH3-H4folate. These substrate-binding domains are ({beta}{alpha})8 barrels packed tightly against one another with their barrel axes perpendicular. The properties of the domain interface suggest that the two barrels remain associated during catalysis. The Hcy and CH3-H4folate substrates are bound at the C termini of their respective barrels in orientations that position them for reaction with cobalamin, but the two active sites are separated by {approx}50 A. To complete the catalytic cycle, the cobalamin-binding domain must travel back and forth between these distant active sites. View this table: TBL1">[in this window] TBL1" onClick="startTarget('TBL1', 500, 400); this.href='TBL1'" onMouseOver="window.status='View table in a separate window'; return true" TARGET="TBL1">[in a new window] Table 1. Data collection and refinement statistics