期刊
STRUCTURE
卷 8, 期 2, 页码 111-122出版社
CELL PRESS
DOI: 10.1016/S0969-2126(00)00087-3
关键词
drug metabolism; epoxide hydrolase; MAD; microsomal epoxide hydrolases; X-ray crystallography
Background: Epoxide hydrolases have important roles in the:defense of cells against potentially harmful epoxides. Conversion of epoxides into less toxic and more easily excreted diets is a universally successful strategy. A number of microorganisms employ the same chemistry to process epoxides for use as carbon sources. Results: The X-ray structure of the epoxide hydrolase from Aspergillus niger was-determined at 3.5 Angstrom resolution using the multiwavelength anomalous dispersion (MAD) method, and then refined at 1.8 Angstrom resolution. There is a dimer consisting of two 44 kDa subunits in the asymmetric unit. Each subunit consists of an alpha/beta hydrolase fold, and a primarily helical lid over the active site; The dimer interface includes lid-lid interactions as well as contributions from an N-terminal meander, The active site contains a classical catalytic triad,and two tyrosines and a glutamic acid residue that are likely to assist in catalysis. Conclusions: The Aspergillus enzyme provides the first structure of an epoxide hydrolase with strong relationships to the most important enzyme of human epoxide metabolism, the microsomal epoxide hydrolase, Differences in active-site residues, especially in components that assist in epoxide ring opening and hydrolysis of the enzyme-substrate intermediate, might explain why-the fungal enzyme attains the greater speeds necessary for an effective metabolic enzyme. The N-terminal domain that is characteristic of microsomal epoxide hydrolases corresponds to a meander that is critical for dimer formation in the Aspergillus enzyme.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据