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5s9o

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Revision as of 15:28, 6 March 2024

CRYSTAL STRUCTURE OF THE HUMAN BRD2 BD1 BROMODOMAIN IN COMPLEX WITH 9-(cyclopropylmethyl)-7-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-3-(3,5-dimethyl-1,2-oxazol-4-yl)-9H-carbazole-1-carboxamide

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Retrieved from "http://52.214.119.220/wiki/index.php/5s9o"

Categories: Homo sapiens | Large Structures | Sheriff S

@@ Line 3: / Line 3: @@
 <StructureSection load='5s9o' size='340' side='right'caption='[[5s9o]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5s9o]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5S9O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5s9o]] is a 2 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=5S9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5S9O FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=YW1:9-(cyclopropylmethyl)-7-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-3-(3,5-dimethyl-1,2-oxazol-4-yl)-9H-carbazole-1-carboxamide'>YW1</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]] 2.49&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=YW1:9-(cyclopropylmethyl)-7-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-3-(3,5-dimethyl-1,2-oxazol-4-yl)-9H-carbazole-1-carboxamide'>YW1</scene></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=5s9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s9o OCA], [https://pdbe.org/5s9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5s9o RCSB], [https://www.ebi.ac.uk/pdbsum/5s9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5s9o ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>
-Inhibition of the bromodomain and extra-terminal (BET) family of adaptor proteins is an attractive strategy for targeting transcriptional regulation of key oncogenes, such as c-MYC. Starting with the screening hit 1, a combination of structure-activity relationship and protein structure-guided drug design led to the discovery of a differently oriented carbazole 9 with favorable binding to the tryptophan, proline, and phenylalanine (WPF) shelf conserved in the BET family. Identification of an additional lipophilic pocket and functional group optimization to optimize pharmacokinetic (PK) properties culminated in the discovery of 18 (BMS-986158) with excellent potency in binding and functional assays. On the basis of its favorable PK profile and robust in vivo activity in a panel of hematologic and solid tumor models, BMS-986158 was selected as a candidate for clinical evaluation.
-Discovery and Preclinical Pharmacology of an Oral Bromodomain and Extra-Terminal (BET) Inhibitor Using Scaffold-Hopping and Structure-Guided Drug Design.,Gavai AV, Norris D, Delucca G, Tortolani D, Tokarski JS, Dodd D, O'Malley D, Zhao Y, Quesnelle C, Gill P, Vaccaro W, Huynh T, Ahuja V, Han WC, Mussari C, Harikrishnan L, Kamau M, Poss M, Sheriff S, Yan C, Marsilio F, Menard K, Wen ML, Rampulla R, Wu DR, Li J, Zhang H, Li P, Sun D, Yip H, Traeger SC, Zhang Y, Mathur A, Zhang H, Huang C, Yang Z, Ranasinghe A, Everlof G, Raghavan N, Tye CK, Wee S, Hunt JT, Vite G, Westhouse R, Lee FY J Med Chem. 2021 Oct 14;64(19):14247-14265. doi: 10.1021/acs.jmedchem.1c00625., Epub 2021 Sep 20. PMID:34543572<ref>PMID:34543572</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 5s9o" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Sheriff, S]]
+[[Category: Sheriff S]]
-[[Category: Acetyl-lysine recognition]]
-[[Category: Acetylated histone h4]]
-[[Category: Cell cycle]]
-[[Category: Helical bundle]]
-[[Category: Nucleus]]
-[[Category: Transcription-transcription inhibitor complex]]

5s9o

From Proteopedia

Revision as of 15:28, 6 March 2024

CRYSTAL STRUCTURE OF THE HUMAN BRD2 BD1 BROMODOMAIN IN COMPLEX WITH 9-(cyclopropylmethyl)-7-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-3-(3,5-dimethyl-1,2-oxazol-4-yl)-9H-carbazole-1-carboxamide

Structural highlights

Function

References

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