1vj5

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spinqualitylabelsall models 1vj5, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Human soluble Epoxide Hydrolase- N-cyclohexyl-N'-(4-iodophenyl)urea complex

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The X-ray crystal structure of human soluble epoxide hydrolase (sEH) has, been determined at 2.6 A resolution, revealing a domain-swapped quaternary, structure identical to that observed for the murine enzyme [Argiriadi, M., A., Morisseau, C., Hammock, B. D., and Christianson, D. W. (1999) Proc., Natl. Acad. Sci. U.S.A. 96, 10637-10642]. As with the murine enzyme, the, epoxide hydrolytic mechanism of the human enzyme proceeds through an, alkyl-enzyme intermediate with Asp-333 in the C-terminal domain. The, structure of the human sEH complex with N-cyclohexyl-N'-(iodophenyl)urea, (CIU) has been determined at 2.35 A resolution. Tyr-381 and Tyr-465 donate, hydrogen bonds to the alkylurea carbonyl group of CIU, consistent with the, proposed roles of these residues as proton donors in the first step of, catalysis. The N-terminal domain of mammalian sEH contains a 15 A deep, cleft, but its biological function is unclear. Recent experiments, demonstrate that the N-terminal domain of human sEH catalyzes the, metal-dependent hydrolysis of phosphate esters [Cronin, A., Mowbray, S., Durk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F., and Arand, M. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 1552-1557; Newman, J. W., Morisseau, C., Harris, T. R., and Hammock, B. D. (2003) Proc. Natl. Acad., Sci. U.S.A. 100, 1558-1563]. The binding of Mg(2+)-HPO4(2-) to the, N-terminal domain of human sEH in its CIU complex reveals structural, features relevant to those of the enzyme-substrate complex in the, phosphatase reaction.

Disease

Known disease associated with this structure: Hypercholesterolemia, familial, due to LDLR defect, modifier of OMIM:[132811]

About this Structure

1VJ5 is a Single protein structure of sequence from Homo sapiens with MG, PO4, P6G and CIU as ligands. Active as Microsomal epoxide hydrolase, with EC number 3.3.2.9 Full crystallographic information is available from OCA.

Reference

Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis., Gomez GA, Morisseau C, Hammock BD, Christianson DW, Biochemistry. 2004 Apr 27;43(16):4716-23. PMID:15096040

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