6cks

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of BRD4 with QC4956

Structural highlights

6cks is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.72Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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.^[1] ^[2]

Function

BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

Publication Abstract from PubMed

The bromodomain and extra-terminal (BET) family of epigenetic proteins has attracted considerable attention in drug discovery given its involvement in regulating gene transcription. Screening a focused small molecule library based on the bromodomain pharmacophore resulted in the identification of 2-methylisoquinoline-1-one as a novel BET bromodomain-binding motif. Structure guided SAR exploration resulted in >10,000-fold potency improvement for the BRD4-BD1 bromodomain. Lead compounds exhibited excellent potencies in both biochemical and cellular assays in MYC-dependent cell lines. Compound 36 demonstrated good physicochemical properties and promising exposure levels in exploratory PK studies.

Design, synthesis and biological evaluation of novel 4-phenylisoquinolinone BET bromodomain inhibitors.,Bennett MJ, Wu Y, Boloor A, Matuszkiewicz J, O'Connell SM, Shi L, Stansfield RK, Del Rosario JR, Veal JM, Hosfield DJ, Xu J, Kaldor SW, Stafford JA, Betancort JM Bioorg Med Chem Lett. 2018 Apr 10. pii: S0960-894X(18)30325-1. doi:, 10.1016/j.bmcl.2018.04.016. PMID:29657099^[3]

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

References

↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
↑ Bennett MJ, Wu Y, Boloor A, Matuszkiewicz J, O'Connell SM, Shi L, Stansfield RK, Del Rosario JR, Veal JM, Hosfield DJ, Xu J, Kaldor SW, Stafford JA, Betancort JM. Design, synthesis and biological evaluation of novel 4-phenylisoquinolinone BET bromodomain inhibitors. Bioorg Med Chem Lett. 2018 Apr 10. pii: S0960-894X(18)30325-1. doi:, 10.1016/j.bmcl.2018.04.016. PMID:29657099 doi:http://dx.doi.org/10.1016/j.bmcl.2018.04.016

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cks"

Categories: Homo sapiens | Large Structures | Hosfield DJ

@@ Line 1: / Line 1: @@
 ==Crystal Structure of BRD4 with QC4956==
-<StructureSection load='6cks' size='340' side='right' caption='[[6cks]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
+<StructureSection load='6cks' size='340' side='right'caption='[[6cks]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6cks]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CKS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CKS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6cks]] 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=6CKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CKS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F5Y:4-[5-(ethylsulfonyl)-2-methoxyphenyl]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-one'>F5Y</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]] 1.72&#8491;</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=6cks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cks OCA], [http://pdbe.org/6cks PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cks RCSB], [http://www.ebi.ac.uk/pdbsum/6cks PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cks ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F5Y:4-[5-(ethylsulfonyl)-2-methoxyphenyl]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-one'>F5Y</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=6cks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cks OCA], [https://pdbe.org/6cks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cks RCSB], [https://www.ebi.ac.uk/pdbsum/6cks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cks ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://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>
+[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 ==
-[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
+[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 ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 6cks" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Hosfield, D J]]
+[[Category: Homo sapiens]]
-[[Category: Acetyllysine]]
+[[Category: Large Structures]]
-[[Category: Brd4]]
+[[Category: Hosfield DJ]]
-[[Category: Epigenetic]]
-[[Category: Gene regulation-inhibitor complex]]

6cks

From Proteopedia

Current revision

Crystal Structure of BRD4 with QC4956

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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