4flp: Difference between revisions

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-[[Image:4flp.png|left|200px]]
+==Crystal Structure of the first bromodomain of human BRDT in complex with the inhibitor JQ1==
+<StructureSection load='4flp' size='340' side='right' caption='[[4flp]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4flp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FLP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FLP FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JQ1:(6S)-6-(2-TERT-BUTOXY-2-OXOETHYL)-4-(4-CHLOROPHENYL)-2,3,9-TRIMETHYL-6,7-DIHYDROTHIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A][1,4]DIAZEPIN-10-IUM'>JQ1</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2rfj|2rfj]]</td></tr>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRDT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4flp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4flp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4flp RCSB], [http://www.ebi.ac.uk/pdbsum/4flp PDBsum]</span></td></tr>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A pharmacologic approach to male contraception remains a longstanding challenge in medicine. Toward this objective, we explored the spermatogenic effects of a selective small-molecule inhibitor (JQ1) of the bromodomain and extraterminal (BET) subfamily of epigenetic reader proteins. Here, we report potent inhibition of the testis-specific member BRDT, which is essential for chromatin remodeling during spermatogenesis. Biochemical and crystallographic studies confirm that occupancy of the BRDT acetyl-lysine binding pocket by JQ1 prevents recognition of acetylated histone H4. Treatment of mice with JQ1 reduced seminiferous tubule area, testis size, and spermatozoa number and motility without affecting hormone levels. Although JQ1-treated males mate normally, inhibitory effects of JQ1 evident at the spermatocyte and round spermatid stages cause a complete and reversible contraceptive effect. These data establish a new contraceptive that can cross the blood:testis boundary and inhibit bromodomain activity during spermatogenesis, providing a lead compound targeting the male germ cell for contraception. PAPERCLIP:
-{{STRUCTURE_4flp|  PDB=4flp  |  SCENE=  }}
+Small-Molecule Inhibition of BRDT for Male Contraception.,Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE Cell. 2012 Aug 17;150(4):673-684. PMID:22901802<ref>PMID:22901802</ref>
-===Crystal Structure of the first bromodomain of human BRDT in complex with the inhibitor JQ1===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_22901802}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-[[4flp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FLP OCA].
+</StructureSection>
-==Reference==
-<ref group="xtra">PMID:022901802</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
 [[Category: Arrowsmith, C H.]]