5tl9: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,037 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,037 edits
No edit summary
Line 3: Line 3:
<StructureSection load='5tl9' size='340' side='right'caption='[[5tl9]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
<StructureSection load='5tl9' size='340' side='right'caption='[[5tl9]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5tl9]] 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=5TL9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TL9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5tl9]] 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=5TL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TL9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7DN:2-{2-[(1S,2S)-2-{[1-(8-METHYLQUINOLIN-2-YL)PIPERIDINE-4-CARBONYL]AMINO}CYCLOPENTYL]ETHYL}BENZOIC+ACID'>7DN</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=JZR:HEXYL+BETA-D-GLUCOPYRANOSIDE'>JZR</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7DN:2-{2-[(1S,2S)-2-{[1-(8-METHYLQUINOLIN-2-YL)PIPERIDINE-4-CARBONYL]AMINO}CYCLOPENTYL]ETHYL}BENZOIC+ACID'>7DN</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=JZR:HEXYL+BETA-D-GLUCOPYRANOSIDE'>JZR</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tl9 OCA], [https://pdbe.org/5tl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tl9 RCSB], [https://www.ebi.ac.uk/pdbsum/5tl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tl9 ProSAT]</span></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=5tl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tl9 OCA], [http://pdbe.org/5tl9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tl9 RCSB], [http://www.ebi.ac.uk/pdbsum/5tl9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tl9 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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 ==
We describe a novel class of acidic mPGES-1 inhibitors with nanomolar enzymatic and human whole blood (HWB) potency. Rational design in conjunction with structure-based design led initially to the identification of anthranilic acid 5, an mPGES-1 inhibitor with micromolar HWB potency. Structural modifications of 5 improved HWB potency by over 1000x, reduced CYP2C9 single point inhibition, and improved rat clearance, which led to the selection of [(cyclopentyl)ethyl]benzoic acid compound 16 for clinical studies. Compound 16 showed an IC80 of 24nM for inhibition of PGE2 formation in vitro in LPS-stimulated HWB. A single oral dose resulted in plasma concentrations of 16 that exceeded its HWB IC80 in both rat (5mg/kg) and dog (3mg/kg) for over twelve hours.
 
Discovery and characterization of [(cyclopentyl)ethyl]benzoic acid inhibitors of microsomal prostaglandin E synthase-1.,Partridge KM, Antonysamy S, Bhattachar SN, Chandrasekhar S, Fisher MJ, Fretland A, Gooding K, Harvey A, Hughes NE, Kuklish SL, Luz JG, Manninen PR, McGee JE, Mudra DR, Navarro A, Norman BH, Quimby SJ, Schiffler MA, Sloan AV, Warshawsky AM, Weller JM, York JS, Yu XP Bioorg Med Chem Lett. 2017 Mar 15;27(6):1478-1483. doi:, 10.1016/j.bmcl.2016.11.011. Epub 2016 Nov 7. PMID:28190634<ref>PMID:28190634</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5tl9" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Line 28: Line 17:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Prostaglandin-E synthase]]
[[Category: Antonysamy S]]
[[Category: Antonysamy, S]]
[[Category: Fisher M]]
[[Category: Fisher, M]]
[[Category: Luz JG]]
[[Category: Luz, J G]]
[[Category: Partridge K]]
[[Category: Partridge, K]]
[[Category: Alpha helix]]
[[Category: Enzyme]]
[[Category: Integral membrane protein]]
[[Category: Membrane protein]]
[[Category: Mpges1 - ligand 0]]
[[Category: Prostaglandin]]
[[Category: Transferase]]
Retrieved from "https://proteopedia.org/5tl9"