Sandbox Reserved 714

X-ray crystal structure of hsEH: Asymmetric unit, 1s8o

Ligands:

Gene:

Activity:

Hydrolase, with EC number and 3.3.2.10 3.3.2.9 and 3.3.2.10

Related:

Structural annotation:
Resources:	InterPro : Ipr011945, Ipr005834, Ipr006402, Ipr003089, Ipr005833, Ipr000639, Ipr000073 Pfam : PF00702, PF00561 SCOP : d1s8oa2, d1s8oa1 UniProt : P34913

Functional annotation:
Cellular component:	peroxisome soluble fraction cytosol cytoplasm
Biological process:	oxygen and reactive oxygen species metabolic process cellular calcium ion homeostasis inflammatory response response to toxin metabolic process positive regulation of vasodilation xenobiotic metabolic process drug metabolic process aromatic compound metabolic process aromatic compound catabolic process regulation of blood pressure
Molecular function:	magnesium ion binding catalytic activity epoxide hydrolase activity metal ion binding hydrolase activity protein homodimerization activity

Evolutionary conservation:

Toggle Conservation Colors:	Rows = identical sequences:
Further Information:	Caveats, Explanation, Complete Results at ConSurfDB

Resources:

FirstGlance, OCA, RCSB, PDBsum

Coordinates:

save as pdb, mmCIF, xml

Human Soluble Epoxide Hydrolase: Biological assembly, 1s8o

OverviewOverview

Structure

The Human soluble Epoxide hydrolase is a protein of 555 residues. In vivo, it exists under the form of a homodimer, with a monomeric unit of 62,5 kDa. Each subunit has , linked by a proline-rich section.

Mechanism

The C-terminal domain is called Cytosolic epoxide hydrolase 2: it catalyzes the trans-addition of water to epoxides in order to product glycols^[1]. The is made of five residues. The 3D structure of this active site is maintained by hydrogen bonds, including those created by D496. The two tyrosines (Y383 and Y466) assist the proper positioning of the substrate by polarizing it, thanks to their hydroxyl groups. D335 plays the role of the nucleophilic acid. Finally, H524 plays the role of a base in order to release the final product.

The N-terminal domain is responsible of the Mg²⁺ dependant hydrolysis of p-nitrophenyl phosphate ^[2]. Its contains several conserved aspartates in phosphatases and phosphonatases: D9, D11, D184 and D185. This enzymatic activity is Mg²⁺ dependant, because the structure of the active site is in its optimal conformation when the cation makes coordination interactions. When the catalytic activity of the N-term domain is available, Magnesium is octahedrally coordinated with the four aspartates, one water molecule and the phosphate belonging to the substrate.

Inhibitors

External ressourcesExternal ressources

ReferencesReferences

↑ Morisseau C, Hammock BD. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu Rev Pharmacol Toxicol. 2005;45:311-33. PMID:15822179 doi:10.1146/annurev.pharmtox.45.120403.095920
↑ Gomez GA, Morisseau C, Hammock BD, Christianson DW. Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry. 2004 Apr 27;43(16):4716-23. PMID:15096040 doi:10.1021/bi036189j

Proteopedia Page Contributors and EditorsProteopedia Page Contributors and Editors

DUTREUX Fabien, BONHOURE Anna

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Fabien Dutreux, Anna Bonhoure

[1] Morisseau C, Hammock BD. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu Rev Pharmacol Toxicol. 2005;45:311-33. PMID:15822179 doi:10.1146/annurev.pharmtox.45.120403.095920

[2] Gomez GA, Morisseau C, Hammock BD, Christianson DW. Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry. 2004 Apr 27;43(16):4716-23. PMID:15096040 doi:10.1021/bi036189j

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