7mcf
From Proteopedia
(Difference between revisions)
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==CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX WITH 2-{3-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-fluoro-5-[(S)-(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-5H-pyrido[3,2-b]indol-7-yl}propan-2-ol== | ==CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX WITH 2-{3-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-fluoro-5-[(S)-(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-5H-pyrido[3,2-b]indol-7-yl}propan-2-ol== | ||
| - | <StructureSection load='7mcf' size='340' side='right'caption='[[7mcf]]' scene=''> | + | <StructureSection load='7mcf' size='340' side='right'caption='[[7mcf]], [[Resolution|resolution]] 2.19Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MCF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7mcf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MCF FirstGlance]. <br> |
| - | </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=7mcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mcf OCA], [https://pdbe.org/7mcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mcf RCSB], [https://www.ebi.ac.uk/pdbsum/7mcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mcf ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YX4:2-{3-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-fluoro-5-[(S)-(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-5H-pyrido[3,2-b]indol-7-yl}propan-2-ol'>YX4</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([https://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=7mcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mcf OCA], [https://pdbe.org/7mcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mcf RCSB], [https://www.ebi.ac.uk/pdbsum/7mcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mcf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We describe our efforts to identify structurally diverse leads in the triazole-containing N1-carboline series of bromodomain and extra-terminal inhibitors. Replacement of the N5 "cap" phenyl moiety with various heteroaryls, coupled with additional modifications to the carboline core, provided analogs with similar potency, improved pharmacokinetic properties, and increased solubility compared to our backup lead, BMS-986225 (2). Rapid SAR exploration was enabled by a convergent, synthetic route. These efforts provided a potent BET inhibitor, 3-fluoropyridyl 12, that demonstrated robust efficacy in a multiple myeloma mouse tumor model at 1 mg/kg. | ||
| + | |||
| + | Development of BET inhibitors as potential treatments for cancer: A search for structural diversity.,Hill MD, Fang H, Tokarski J, Fanslau C, Haarhoff Z, Huang C, Kramer M, Menard K, Monereau L, Morrison J, Ranasinghe A, Shields EE, Tye CK, Westhouse R, Everlof G, Sheriff S, Yan C, Marsilio F, Zhang L, Zvyaga T, Lee F, Gavai AV, Degnan AP Bioorg Med Chem Lett. 2021 May 13;44:128108. doi: 10.1016/j.bmcl.2021.128108. PMID:33991625<ref>PMID:33991625</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7mcf" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Sheriff S]] | + | [[Category: Sheriff, S]] |
| + | [[Category: Brd4]] | ||
| + | [[Category: Bromodomain containing protein 4]] | ||
| + | [[Category: Bromodomain-containing protein 4 isoform long]] | ||
| + | [[Category: Cap]] | ||
| + | [[Category: Cell cycle]] | ||
| + | [[Category: Hunk1]] | ||
| + | [[Category: Mcap]] | ||
| + | [[Category: Mitotic chromosome associated protein sgc]] | ||
Revision as of 14:52, 2 June 2021
CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX WITH 2-{3-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-fluoro-5-[(S)-(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-5H-pyrido[3,2-b]indol-7-yl}propan-2-ol
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