5jct
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Human Pirin in complex with a Chemical Probe pyrrolidine 24== | |
| + | <StructureSection load='5jct' size='340' side='right' caption='[[5jct]], [[Resolution|resolution]] 1.73Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5jct]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JCT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JCT FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6JQ:N-{5-[(2,3-DIHYDRO-1,4-BENZODIOXINE-6-CARBONYL)AMINO]-2-METHYLPHENYL}-2-[3-(PYRROLIDIN-1-YL)PROPYL]QUINOLINE-6-CARBOXAMIDE'>6JQ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Quercetin_2,3-dioxygenase Quercetin 2,3-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.24 1.13.11.24] </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=5jct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jct OCA], [http://pdbe.org/5jct PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jct RCSB], [http://www.ebi.ac.uk/pdbsum/5jct PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jct ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PIR_HUMAN PIR_HUMAN]] Possible transcriptional coregulator. May contribute to the regulation of cellular processes via its interaction with BCL3. May be required for efficient terminal myeloid maturation of hematopoietic cells. May play a role in the regulation of cell migration. May promote apoptosis when overexpressed. Has quercetin 2,3-dioxygenase activity (in vitro).<ref>PMID:9079676</ref> <ref>PMID:17288615</ref> <ref>PMID:20010624</ref> <ref>PMID:20711196</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell-based SAR and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography. | ||
| - | + | Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.,Cheeseman MD, Chessum NE, Rye CS, Pasqua AE, Tucker MJ, Wilding B, Evans LE, Lepri S, Richards M, Sharp SY, Ali S, Rowlands M, O'Fee L, Miah A, Hayes A, Henley AT, Powers M, Te Poele R, De Billy E, Pellegrino L, Raynaud F, Burke R, van Montfort RL, Eccles SA, Workman P, Jones K J Med Chem. 2017 Jan 12;60(1):180-201. doi: 10.1021/acs.jmedchem.6b01055. Epub, 2016 Dec 22. PMID:28004573<ref>PMID:28004573</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5jct" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Quercetin 2,3-dioxygenase]] | ||
| + | [[Category: Ali, S]] | ||
| + | [[Category: Montfort, R van]] | ||
| + | [[Category: Beta-barrel fold]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Cupin]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Oxidoreductase]] | ||
Revision as of 16:28, 18 January 2017
Crystal Structure of Human Pirin in complex with a Chemical Probe pyrrolidine 24
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