4jnc

From Proteopedia

(Difference between revisions)

Revision as of 11:25, 24 November 2022

Soluble Epoxide Hydrolase complexed with a carboxamide inhibitor

Structural highlights

4jnc is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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

1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[[4-bromo-2-(trifluoromethoxy) ]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models.

Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase.,Thalji RK, McAtee JJ, Belyanskaya S, Brandt M, Brown GD, Costell MH, Ding Y, Dodson JW, Eisennagel SH, Fries RE, Gross JW, Harpel MR, Holt DA, Israel DI, Jolivette LJ, Krosky D, Li H, Lu Q, Mandichak T, Roethke T, Schnackenberg CG, Schwartz B, Shewchuk LM, Xie W, Behm DJ, Douglas SA, Shaw AL, Marino JP Jr Bioorg Med Chem Lett. 2013 Jun 15;23(12):3584-8. doi: 10.1016/j.bmcl.2013.04.019., Epub 2013 Apr 16. PMID:23664879^[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
↑ Thalji RK, McAtee JJ, Belyanskaya S, Brandt M, Brown GD, Costell MH, Ding Y, Dodson JW, Eisennagel SH, Fries RE, Gross JW, Harpel MR, Holt DA, Israel DI, Jolivette LJ, Krosky D, Li H, Lu Q, Mandichak T, Roethke T, Schnackenberg CG, Schwartz B, Shewchuk LM, Xie W, Behm DJ, Douglas SA, Shaw AL, Marino JP Jr. Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase. Bioorg Med Chem Lett. 2013 Jun 15;23(12):3584-8. doi: 10.1016/j.bmcl.2013.04.019., Epub 2013 Apr 16. PMID:23664879 doi:10.1016/j.bmcl.2013.04.019

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/4jnc"

Categories: Homo sapiens | Large Structures | Shewchuk LM

@@ Line 1: / Line 1: @@
 ==Soluble Epoxide Hydrolase complexed with a carboxamide inhibitor==
-<StructureSection load='4jnc' size='340' side='right' caption='[[4jnc]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
+<StructureSection load='4jnc' size='340' side='right'caption='[[4jnc]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4jnc]] is a 1 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=4JNC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JNC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4jnc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JNC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1LF:1-[4-METHYL-6-(METHYLAMINO)-1,3,5-TRIAZIN-2-YL]-N-[2-(TRIFLUOROMETHYL)BENZYL]PIPERIDINE-4-CARBOXAMIDE'>1LF</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1LF:1-[4-METHYL-6-(METHYLAMINO)-1,3,5-TRIAZIN-2-YL]-N-[2-(TRIFLUOROMETHYL)BENZYL]PIPERIDINE-4-CARBOXAMIDE'>1LF</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jnc OCA], [https://pdbe.org/4jnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jnc RCSB], [https://www.ebi.ac.uk/pdbsum/4jnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jnc ProSAT]</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=4jnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jnc OCA], [http://pdbe.org/4jnc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jnc RCSB], [http://www.ebi.ac.uk/pdbsum/4jnc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jnc ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/HYES_HUMAN 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.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>
+[https://www.uniprot.org/uniprot/HYES_HUMAN 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.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 20: @@
 ==See Also==
-*[[Epoxide hydrolase|Epoxide hydrolase]]
+*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Shewchuk, L M]]
+[[Category: Large Structures]]
-[[Category: Epoxide hydrolase]]
+[[Category: Shewchuk LM]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]

4jnc

From Proteopedia

Revision as of 11:25, 24 November 2022

Soluble Epoxide Hydrolase complexed with a carboxamide inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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