Structure of Aspergillus niger epoxide hydrolase at 1.8 Å resolution:: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases

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.