6fnx: Difference between revisions

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-'''Unreleased structure'''
-The entry 6fnx is ON HOLD
+==FIRST DOMAIN OF HUMAN BROMODOMAIN BRD4 IN COMPLEX WITH INHIBITOR F1==
+<StructureSection load='6fnx' size='340' side='right' caption='[[6fnx]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6fnx]] 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=6FNX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FNX FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DYZ:7-ethyl-3-(phenylmethyl)purine-2,6-dione'>DYZ</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fnx OCA], [http://pdbe.org/6fnx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fnx RCSB], [http://www.ebi.ac.uk/pdbsum/6fnx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fnx 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>
+== Function ==
+[[http://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 ==
+Over the past few decades, hit identification has been greatly facilitated by advances in high-throughput and fragment-based screenings. One major hurdle remaining in drug discovery is process automation of hit-to-lead (H2L) optimization. Here, we report a time and cost-efficient integrated strategy for H2L optimization and partially automated design of potent chemical probes consisting of focused chemical library design and virtual screening coupled with robotic diversity-oriented de novo synthesis and automated in vitro evaluation. The virtual library is generated by combining an activated fragment corresponding to the substructure binding to the target with a collection of functionalized building blocks using in silico-encoded chemical reactions carefully chosen from a list of one-step organic transformations that are relevant in medicinal chemistry. The proof of concept was demonstrated using the optimization of bromodomain inhibitors as a test case, leading to the validation of several compounds with affinity improved by several orders of magnitude.
-Authors: Raux, B., Betzi, S.
+An Integrated Strategy for Lead Optimization based on Fragment Growing: The DOTS (Diversity-Oriented Target-focused Synthesis) Approach.,Hoffer L, Voitovich YV, Raux B, Carrasco K, Muller C, Fedorov AY, Derviaux C, Amouric A, Betzi S, Horvath D, Varnek A, Collette Y, Combes S, Roche P, Morelli X J Med Chem. 2018 Jun 8. doi: 10.1021/acs.jmedchem.8b00653. PMID:29883107<ref>PMID:29883107</ref>
-Description: FIRST DOMAIN OF HUMAN BROMODOMAIN BRD4 IN COMPLEX WITH INHIBITOR F1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6fnx" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Betzi, S]]
 [[Category: Raux, B]]
-[[Category: Betzi, S]]
+[[Category: Bromodomain]]
+[[Category: Dna binding protein]]
+[[Category: Epigenetic reader]]
+[[Category: Histone]]
+[[Category: Inhibitor]]