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4x6x

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Revision as of 07:13, 29 May 2019

Human soluble epoxide hydrolase in complex with a three substituted cyclopropane derivative

Structural highlights

4x6x 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:	4x6y
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

We have previously reported a series of cyclopropyl urea derivatives as potent orally available soluble epoxide hydrolase (sEH) inhibitors. Here, we designed and synthesized three substituted cyclopropane derivatives that occupy all available pockets of sEH catalytic domain. Compound 14 with a diphenyl substituted cyclopropyl moiety showed good sEH inhibitory activity. Co-crystal structure of this compound and human sEH hydrolase catalytic domain revealed enzyme pockets occupied by the phenoxypiperidine part and the diphenyl cyclopropyl moiety. Furthermore, investigation of the phenoxypiperidine part of compound 14 resulted in the discovery of compound 19, which showed potent sEH inhibitory activity (sub-nM sEH IC50 values).

Three-dimensional rational approach to the discovery of potent substituted cyclopropyl urea soluble epoxide hydrolase inhibitors.,Takai K, Chiyo N, Nakajima T, Nariai T, Ishikawa C, Nakatani S, Ikeno A, Yamamoto S, Sone T Bioorg Med Chem Lett. 2015 Apr 15;25(8):1705-8. doi: 10.1016/j.bmcl.2015.02.076. , Epub 2015 Mar 7. PMID:25800114^[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
↑ Takai K, Chiyo N, Nakajima T, Nariai T, Ishikawa C, Nakatani S, Ikeno A, Yamamoto S, Sone T. Three-dimensional rational approach to the discovery of potent substituted cyclopropyl urea soluble epoxide hydrolase inhibitors. Bioorg Med Chem Lett. 2015 Apr 15;25(8):1705-8. doi: 10.1016/j.bmcl.2015.02.076. , Epub 2015 Mar 7. PMID:25800114 doi:http://dx.doi.org/10.1016/j.bmcl.2015.02.076

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/4x6x"

@@ Line 1: / Line 1: @@
 ==Human soluble epoxide hydrolase in complex with a three substituted cyclopropane derivative==
-<StructureSection load='4x6x' size='340' side='right' caption='[[4x6x]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='4x6x' size='340' side='right'caption='[[4x6x]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x6x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x6x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6X FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=S74:3-{4-[(1-{[(1S,2R,3S)-2,3-DIPHENYLCYCLOPROPYL]CARBAMOYL}PIPERIDIN-4-YL)OXY]PHENYL}PROPANOIC+ACID'>S74</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x6y|4x6y]]</td></tr>
+<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=4x6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6x OCA], [http://pdbe.org/4x6x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6x RCSB], [http://www.ebi.ac.uk/pdbsum/4x6x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6x ProSAT]</span></td></tr>
@@ Line 27: / Line 28: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Soluble epoxide hydrolase]]
 [[Category: Chiyo, N]]

4x6x

From Proteopedia

Revision as of 07:13, 29 May 2019

Human soluble epoxide hydrolase in complex with a three substituted cyclopropane derivative

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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