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spinqualitylabelsall models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D load='1s8o' size='350' frame='false' scene=
X-ray crystal structure of hsEH: Asymmetric unit, 1s8o
Ligands:	P6G
Gene:	EPHX2 (Homo sapiens)
Activity:	Hydrolase, with EC number and 3.3.2.10 3.3.2.9 and 3.3.2.10
Related:	1vj5
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

Overview

spinqualitylabelsall models X-ray crystal structure of hsEH (PDB entry 1s8o) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D General structure Reset 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 two catalytic domains, linked by a proline-rich section. Mechanism C-terminal domain The C-terminal domain is called Cytosolic epoxide hydrolase 2: it catalyzes the trans-addition of water to epoxides in order to product glycols. The corresponding reaction equation is the following: Epoxide + H2O ↔ Glycol The active site 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 acts as a nucleophilic acid. Finally, H524 plays the role of a base in order to release the final product. The reaction proceeds in two steps, including the formation of a covalent intermediate. First, the substrate (epoxide) is accepted in the active site and its oxygen forms hydrogen bonds with Y383 and Y466. The oxygen of D335 attacks one of the two carbons included in the epoxide function. As a result, the oxygen of the subtrate takes the hydrogen of the hydroxyl function of Y466: the covalent intermediate is formed, and linked to D335. Then, the oxygen negatively charged belonging to the lateral chain of Y383 attacks the hydrogen of H524. After that, a water molecule enters the active site. The hydroxyl of D335 is therefore renewed, the diol product is created and released. The active site is available for a new catalytic cycle. N-terminal domain The N-terminal domain is responsible of the Mg2+ dependant hydrolysis of dihydroxy lipid phosphates . The specificity of this enzyme has been tested for several lipid molecules, and the best substrate found is the monophosphate of dihydroxy stearic acid (threo-9�/10-phosphonoxy-hydroxy-octadecanoic acid) . Its active site 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.

Proteopedia Page Contributors and Editors

DUTREUX Fabien, BONHOURE Anna