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4kcx

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{{STRUCTURE_4kcx| PDB=4kcx | SCENE= }}
 
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===BRDT in complex with Dinaciclib===
 
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{{ABSTRACT_PUBMED_24007471}}
 
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==Function==
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==BRDT in complex with Dinaciclib==
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[[http://www.uniprot.org/uniprot/BRDT_HUMAN BRDT_HUMAN]] Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.<ref>PMID:9367677</ref> <ref>PMID:15647849</ref> <ref>PMID:22901802</ref>
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<StructureSection load='4kcx' size='340' side='right'caption='[[4kcx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4kcx]] 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=4KCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KCX FirstGlance]. <br>
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</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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QK:3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1-YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1-HYDROXYPYRIDINIUM'>1QK</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4kcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kcx OCA], [https://pdbe.org/4kcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kcx RCSB], [https://www.ebi.ac.uk/pdbsum/4kcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kcx ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BRDT_HUMAN BRDT_HUMAN] Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.<ref>PMID:9367677</ref> <ref>PMID:15647849</ref> <ref>PMID:22901802</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bromodomain-containing proteins are considered atypical kinases, but their potential to interact with kinase inhibitors is unknown. Dinaciclib is a potent inhibitor of cyclin-dependent kinases (CDKs), which recently advanced to Phase III clinical trials for the treatment of leukemia. We determined the crystal structure of dinaciclib in complex with CDK2 at 1.7 A resolution, revealing an elaborate network of binding interactions in the ATP site, which explains the extraordinary potency and selectivity of this inhibitor. Remarkably, dinaciclib also interacted with the acetyl-lysine recognition site of the bromodomain testis-specific protein BRDT, a member of the BET family of bromodomains. The binding mode of dinaciclib to BRDT at 2.0 A resolution suggests that general kinase inhibitors ("hinge binders") possess a previously unrecognized potential to act as protein-protein inhibitors of bromodomains. The findings may provide a new structural framework for the design of next-generation bromodomain inhibitors using the vast chemical space of kinase inhibitors.
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==About this Structure==
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Cyclin-Dependent Kinase Inhibitor Dinaciclib Interacts with the Acetyl-Lysine Recognition Site of Bromodomains.,Martin MP, Olesen SH, Georg GI, Schonbrunn E ACS Chem Biol. 2013 Sep 10. PMID:24007471<ref>PMID:24007471</ref>
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[[4kcx]] is a 2 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=4KCX OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024007471</ref><references group="xtra"/><references/>
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</div>
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[[Category: Human]]
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<div class="pdbe-citations 4kcx" style="background-color:#fffaf0;"></div>
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[[Category: Martin, M P.]]
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== References ==
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[[Category: Schonbrunn, E.]]
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<references/>
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[[Category: Brdt]]
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__TOC__
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[[Category: Bromodomain containing protein testis specific]]
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</StructureSection>
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[[Category: Cell cycle-inhibitor complex]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Martin MP]]
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[[Category: Schonbrunn E]]

Current revision

BRDT in complex with Dinaciclib

PDB ID 4kcx

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