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4kcx

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Revision as of 21:44, 5 August 2016

BRDT in complex with Dinaciclib

Structural highlights

4kcx is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	BRDT (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

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.

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^[4]

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

References

↑ Jones MH, Numata M, Shimane M. Identification and characterization of BRDT: A testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh. Genomics. 1997 Nov 1;45(3):529-34. PMID:9367677 doi:S0888-7543(97)95000-X
↑ Zheng Y, Yuan W, Zhou Z, Xu M, Sha JH. Molecular cloning and expression of a novel alternative splice variant of BRDT gene. Int J Mol Med. 2005 Feb;15(2):315-21. PMID:15647849
↑ Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE. Small-Molecule Inhibition of BRDT for Male Contraception. Cell. 2012 Aug 17;150(4):673-684. PMID:22901802 doi:10.1016/j.cell.2012.06.045
↑ Martin MP, Olesen SH, Georg GI, Schonbrunn E. Cyclin-Dependent Kinase Inhibitor Dinaciclib Interacts with the Acetyl-Lysine Recognition Site of Bromodomains. ACS Chem Biol. 2013 Sep 10. PMID:24007471 doi:10.1021/cb4003283

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kcx"

@@ Line 1: / Line 1: @@
 ==BRDT in complex with Dinaciclib==
 <StructureSection load='4kcx' size='340' side='right' caption='[[4kcx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
 <tr id='gene'><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 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=4kcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kcx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kcx RCSB], [http://www.ebi.ac.uk/pdbsum/4kcx PDBsum]</span></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=4kcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kcx OCA], [http://pdbe.org/4kcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kcx RCSB], [http://www.ebi.ac.uk/pdbsum/4kcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kcx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4kcx" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4kcx

From Proteopedia

Revision as of 21:44, 5 August 2016

BRDT in complex with Dinaciclib

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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