5jct

From Proteopedia

(Difference between revisions)

Revision as of 07:42, 10 June 2020

Crystal Structure of Human Pirin in complex with a Chemical Probe pyrrolidine 24

Structural highlights

5jct is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	PIR (HUMAN)
Activity:	Quercetin 2,3-dioxygenase, with EC number 1.13.11.24
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2] ^[3] ^[4]

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^[5]

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

References

↑ Wendler WM, Kremmer E, Forster R, Winnacker EL. Identification of pirin, a novel highly conserved nuclear protein. J Biol Chem. 1997 Mar 28;272(13):8482-9. PMID:9079676
↑ Gelbman BD, Heguy A, O'Connor TP, Zabner J, Crystal RG. Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis. Respir Res. 2007 Feb 8;8:10. PMID:17288615 doi:http://dx.doi.org/10.1186/1465-9921-8-10
↑ Licciulli S, Cambiaghi V, Scafetta G, Gruszka AM, Alcalay M. Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation. Leukemia. 2010 Feb;24(2):429-37. doi: 10.1038/leu.2009.247. Epub 2009 Dec 10. PMID:20010624 doi:http://dx.doi.org/10.1038/leu.2009.247
↑ Miyazaki I, Simizu S, Okumura H, Takagi S, Osada H. A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. Nat Chem Biol. 2010 Sep;6(9):667-73. Epub 2010 Aug 15. PMID:20711196 doi:10.1038/nchembio.423
↑ 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. Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen. J Med Chem. 2017 Jan 12;60(1):180-201. doi: 10.1021/acs.jmedchem.6b01055. Epub, 2016 Dec 22. PMID:28004573 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b01055

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jct"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Pirin in complex with a Chemical Probe pyrrolidine 24==
-<StructureSection load='5jct' size='340' side='right' caption='[[5jct]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
+<StructureSection load='5jct' size='340' side='right'caption='[[5jct]], [[Resolution|resolution]] 1.73&Aring;' 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>
+<table><tr><td colspan='2'>[[5jct]] 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=5JCT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIR ([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/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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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 ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Quercetin 2,3-dioxygenase]]
 [[Category: Ali, S]]

5jct

From Proteopedia

Revision as of 07:42, 10 June 2020

Crystal Structure of Human Pirin in complex with a Chemical Probe pyrrolidine 24

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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