1vj5
From Proteopedia
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'''Human soluble Epoxide Hydrolase- N-cyclohexyl-N'-(4-iodophenyl)urea complex''' | '''Human soluble Epoxide Hydrolase- N-cyclohexyl-N'-(4-iodophenyl)urea complex''' | ||
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[[Category: Hammock, B D.]] | [[Category: Hammock, B D.]] | ||
[[Category: Morisseau, C.]] | [[Category: Morisseau, C.]] | ||
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Revision as of 09:35, 3 May 2008
Human soluble Epoxide Hydrolase- N-cyclohexyl-N'-(4-iodophenyl)urea complex
Contents |
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. 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 Page seeded by OCA on Sat May 3 12:35:22 2008
