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3ant

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Revision as of 09:53, 4 August 2016

Human soluble epoxide hydrolase in complex with a synthetic inhibitor

Structural highlights

3ant is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3ans
Gene:	EPHX2 (HUMAN)
Activity:	Soluble epoxide hydrolase, with EC number 3.3.2.10
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HYES_HUMAN] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.^[1] ^[2]

Publication Abstract from PubMed

Ligand efficiency is frequently used to evaluate fragment compounds in fragment-based drug discovery. We applied ligand efficiency indices in a conventional virtual screening-initiated lead generation study of soluble epoxide hydrolase inhibitors. From a considerable number of screening hits, we carefully selected a compound exhibiting relatively weak inhibitory activity but high ligand efficiency. This ligand efficiency-guided selection could reveal compounds possessing preferable lead-like characteristics in terms of molecular size and lipophilicity. The following hit-to-lead medicinal chemistry campaign successfully led to a more potent, ADMET-clean, lead-like compound preserving high ligand efficiency. Retrospective analyses, including consideration of the more recently proposed indices of ligand efficiency, shed light on the validity of our hit triage and hit-to-lead studies. The present work proposes a practical methodology for lead generation using the concept of ligand efficiency.

A Practical Use of Ligand Efficiency Indices Out of the Fragment-Based Approach: Ligand Efficiency-Guided Lead Identification of Soluble Epoxide Hydrolase Inhibitors.,Tanaka D, Tsuda Y, Shiyama T, Nishimura T, Chiyo N, Tominaga Y, Sawada N, Mimoto T, Kusunose N J Med Chem. 2010 Dec 30. PMID:21192659^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1552-7. Epub 2003 Feb 6. PMID:12574508 doi:10.1073/pnas.0437829100
↑ 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
↑ Tanaka D, Tsuda Y, Shiyama T, Nishimura T, Chiyo N, Tominaga Y, Sawada N, Mimoto T, Kusunose N. A Practical Use of Ligand Efficiency Indices Out of the Fragment-Based Approach: Ligand Efficiency-Guided Lead Identification of Soluble Epoxide Hydrolase Inhibitors. J Med Chem. 2010 Dec 30. PMID:21192659 doi:10.1021/jm101273e

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ant"

@@ Line 1: / Line 1: @@
 ==Human soluble epoxide hydrolase in complex with a synthetic inhibitor==
 <StructureSection load='3ant' size='340' side='right' caption='[[3ant]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPHX2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Soluble_epoxide_hydrolase Soluble epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.10 3.3.2.10] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ant FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ant OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ant RCSB], [http://www.ebi.ac.uk/pdbsum/3ant PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ant FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ant OCA], [http://pdbe.org/3ant PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ant RCSB], [http://www.ebi.ac.uk/pdbsum/3ant PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ant ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3ant" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Epoxide hydrolase|Epoxide hydrolase]]
 == References ==
 <references/>

3ant

From Proteopedia

Revision as of 09:53, 4 August 2016

Human soluble epoxide hydrolase in complex with a synthetic inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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