PDBsum entry 1vj5

Hydrolase

PDB id: 1vj5

Contents

Protein chain

547 a.a. *

Ligands

PO4

P6G

CIU

Metals

_MG

Waters ×229

* Residue conservation analysis

PDB id:

1vj5

Name:

Hydrolase

Title:

Human soluble epoxide hydrolase- n-cyclohexyl-n'-(4-iodophenyl)urea complex

Structure:

Epoxide hydrolase 2, cytoplasmic. Chain: a. Synonym: hseh. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ephx2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: high five.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.35Å R-factor: 0.217 R-free: 0.266

Authors:

G.A.Gomez,C.Morisseau,B.D.Hammock,D.W.Christianson

Key ref:

G.A.Gomez et al. (2004). Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry, 43, 4716-4723. PubMed id: 15096040 DOI: 10.1021/bi036189j

Date:

03-Feb-04 Release date: 27-Apr-04

Protein chain

P34913  (HYES_HUMAN) -  Bifunctional epoxide hydrolase 2 from Homo sapiens

Seq: 555 a.a.

Struc: 547 a.a.

Enzyme reactions

• Enzyme class 2: E.C.3.1.3.76 - lipid-phosphate phosphatase.
• Reaction: (9S,10S)-10-hydroxy-9-(phosphooxy)octadecanoate + H2O = (9S,10S)-9,10- dihydroxyoctadecanoate + phosphate

(9S,10S)-10-hydroxy-9-(phosphooxy)octadecanoate + H2O = (9S,10S)-9,10- dihydroxyoctadecanoate + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

• Cofactor: Mg(2+)
• Enzyme class 3: E.C.3.3.2.10 - soluble epoxide hydrolase.
• Reaction: an epoxide + H2O = an ethanediol

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi036189j

Biochemistry 43:4716-4723 (2004)

PubMed id: 15096040

Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis.

G.A.Gomez, C.Morisseau, B.D.Hammock, D.W.Christianson.

ABSTRACT

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., Dürk, 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.