4yl3: Difference between revisions

Revision as of 08:17, 3 May 2023

Crystal Structures of mPGES-1 Inhibitor Complexes

Structural highlights

4yl3 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:	4U9, BOG, GSH, PG4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTGES_HUMAN Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).^[1]

Publication Abstract from PubMed

Microsomal prostaglandin E synthase 1 (mPGES-1) is an alpha-helical homotrimeric integral membrane inducible enzyme that catalyzes the formation of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). Inhibition of mPGES-1 has been proposed as a therapeutic strategy for the treatment of pain, inflammation, and some cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the potential circumvention of cardiovascular risks associated with anti-inflammatory cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway downstream of PGH2 synthesis and avoiding suppression of antithrombotic prostacyclin production. We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to understand their structure-activity relationships and provide a framework for the rational design of improved molecules. In addition, we developed a light-scattering-based thermal stability assay to identify molecules for crystallographic studies.

Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics.,Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D, Yu XP, Chandrasekhar S, Backer R, Zhang A, Russell M, Chang SS, Harvey A, Sloan AV, Fisher MJ J Med Chem. 2015 May 20. PMID:25961169^[2]

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

References

↑ Jegerschold C, Pawelzik SC, Purhonen P, Bhakat P, Gheorghe KR, Gyobu N, Mitsuoka K, Morgenstern R, Jakobsson PJ, Hebert H. Structural basis for induced formation of the inflammatory mediator prostaglandin E2. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11110-5. Epub 2008 Aug 5. PMID:18682561 doi:0802894105
↑ Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D, Yu XP, Chandrasekhar S, Backer R, Zhang A, Russell M, Chang SS, Harvey A, Sloan AV, Fisher MJ. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics. J Med Chem. 2015 May 20. PMID:25961169 doi:https://dx.doi.org/10.1021/acs.jmedchem.5b00330

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Jegerschold C, Pawelzik SC, Purhonen P, Bhakat P, Gheorghe KR, Gyobu N, Mitsuoka K, Morgenstern R, Jakobsson PJ, Hebert H. Structural basis for induced formation of the inflammatory mediator prostaglandin E2. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11110-5. Epub 2008 Aug 5. PMID:18682561 doi:0802894105

[2] Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D, Yu XP, Chandrasekhar S, Backer R, Zhang A, Russell M, Chang SS, Harvey A, Sloan AV, Fisher MJ. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics. J Med Chem. 2015 May 20. PMID:25961169 doi:https://dx.doi.org/10.1021/acs.jmedchem.5b00330

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='4yl3' size='340' side='right'caption='[[4yl3]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4yl3]] 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=4YL3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YL3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4yl3]] 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=4YL3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YL3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4U9:5-[4-BROMO-2-(2-CHLORO-6-FLUOROPHENYL)-1H-IMIDAZOL-5-YL]-2-{[4-(TRIFLUOROMETHYL)PHENYL]ETHYNYL}PYRIDINE'>4U9</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4U9:5-[4-BROMO-2-(2-CHLORO-6-FLUOROPHENYL)-1H-IMIDAZOL-5-YL]-2-{[4-(TRIFLUOROMETHYL)PHENYL]ETHYNYL}PYRIDINE'>4U9</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yk5|4yk5]], [[4yl0|4yl0]], [[4yl1|4yl1]]</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=4yl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yl3 OCA], [https://pdbe.org/4yl3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yl3 RCSB], [https://www.ebi.ac.uk/pdbsum/4yl3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yl3 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTGES, MGST1L1, MPGES1, PGES, PIG12 ([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/Prostaglandin-E_synthase Prostaglandin-E synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.99.3 5.3.99.3] </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=4yl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yl3 OCA], [http://pdbe.org/4yl3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yl3 RCSB], [http://www.ebi.ac.uk/pdbsum/4yl3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yl3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PTGES_HUMAN PTGES_HUMAN]] Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).<ref>PMID:18682561</ref>
+[https://www.uniprot.org/uniprot/PTGES_HUMAN PTGES_HUMAN] Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).<ref>PMID:18682561</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Prostaglandin-E synthase]]
+[[Category: Antonysamy S]]
-[[Category: Antonysamy, S]]
+[[Category: Fisher MJ]]
-[[Category: Fisher, M J]]
+[[Category: Kuklish SL]]
-[[Category: Kuklish, S L]]
+[[Category: Luz JG]]
-[[Category: Luz, J G]]
-[[Category: Inflammation]]
-[[Category: Inhibitor]]
-[[Category: Isomerase-isomerase inhibitor complex]]
-[[Category: Prostaglandin]]

4yl3: Difference between revisions

Revision as of 08:17, 3 May 2023

Crystal Structures of mPGES-1 Inhibitor Complexes

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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