Sandbox Reserved 714

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Line 38: Line 38:
9/10-phosphonoxy-hydroxy-octadecanoate + H<sub>2</sub>O ↔ 9/10-dihydroxy-octadecanoate + phosphate
9/10-phosphonoxy-hydroxy-octadecanoate + H<sub>2</sub>O ↔ 9/10-dihydroxy-octadecanoate + phosphate
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Its <scene name='Sandbox_Reserved_714/Nter_activesite/1'>active site</scene> contains several conserved aspartates in phosphatases and phosphonatases (belonging to the family of haloacid dehalogenase): D9, D11, D184 and D185. This enzymatic activity is Mg<sup>2+</sup> 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. We can note that Mg<sup>2+</sup> is not directly involved in the catalytic mechanism, and all its interactions with the active site remain during the hydrolysis. Its single role consists in maintaining the three-dimensional structure of the active site.
+
Its <scene name='Sandbox_Reserved_714/Nter_activesite/1'>active site</scene> contains several conserved aspartates in phosphatases and phosphonatases: D9, D11, D184 and D185. This enzymatic activity is Mg<sup>2+</sup> 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. We can note that Mg<sup>2+</sup> is not directly involved in the catalytic mechanism, and all its interactions with the active site remain during the hydrolysis. Its single role consists in maintaining the three-dimensional structure of the active site.
First, the oxygen on the lateral chain of D9 attacks the phosphate. After the addition of a proton H<sub>+</sub>, the product with its two hydroxyl functions is released, while the phosphate is still linked to D9. Then, a waters molecule binds the phosphate, breaking its bond with the aspartate. Therefore the phosphate can be finally released and the active site can accept a lipid again and start a new catalytic cycle.
First, the oxygen on the lateral chain of D9 attacks the phosphate. After the addition of a proton H<sub>+</sub>, the product with its two hydroxyl functions is released, while the phosphate is still linked to D9. Then, a waters molecule binds the phosphate, breaking its bond with the aspartate. Therefore the phosphate can be finally released and the active site can accept a lipid again and start a new catalytic cycle.

Revision as of 19:48, 2 January 2013

PDB ID 1s8o

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X-ray crystal structure of hsEH: Asymmetric unit, 1s8o
Ligands:
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
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



Human Soluble Epoxide Hydrolase: Biological assembly, 1s8o
Human Soluble Epoxide Hydrolase: Biological assembly, 1s8o

Contents

Overview

X-ray crystal structure of hsEH (PDB entry 1s8o)

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Additional 3D Structures of hsEH

1vj5 - hsEH + N-cyclohexyl-N'-(4-iodophenyl)urea complex

1zd2,1zd3, 1zd4,1zd5 - hsEH + 4-(3-cyclohexyluriedo)-carboxylic acids

3ant - Hydrolase domain + synthetic inhibitor

3pdc - Hydrolase domain + benzoxazole inhibitor

External ressources

Protein Data Bank entry on 1S8O

Uniprot link on Bifunctional epoxyde hydrolase 2

Wikipedia page on Epoxyde hydrolase 2

References

  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
  3. Newman JW, Morisseau C, Harris TR, Hammock BD. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1558-63. Epub 2003 Feb 6. PMID:12574510 doi:10.1073/pnas.0437724100

Proteopedia Page Contributors and Editors

DUTREUX Fabien, BONHOURE Anna

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