7ubo

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==Crystal Structure of the first bromodomain of human BRDT in complex with the inhibitor CCD-956==
==Crystal Structure of the first bromodomain of human BRDT in complex with the inhibitor CCD-956==
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<StructureSection load='7ubo' size='340' side='right'caption='[[7ubo]]' scene=''>
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<StructureSection load='7ubo' size='340' side='right'caption='[[7ubo]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UBO FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7ubo]] is a 4 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=7UBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UBO FirstGlance]. <br>
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</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=7ubo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ubo OCA], [https://pdbe.org/7ubo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ubo RCSB], [https://www.ebi.ac.uk/pdbsum/7ubo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ubo ProSAT]</span></td></tr>
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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]] 1.82&#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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MJN:N-[(2R)-1-(methylamino)-3-{1-[(4-methyl-2-oxo-1,2-dihydroquinolin-6-yl)acetyl]piperidin-4-yl}-1-oxopropan-2-yl]-5-phenylpyridine-2-carboxamide'>MJN</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=7ubo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ubo OCA], [https://pdbe.org/7ubo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ubo RCSB], [https://www.ebi.ac.uk/pdbsum/7ubo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ubo ProSAT]</span></td></tr>
</table>
</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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SignificanceBET bromodomain inhibition is therapeutic in multiple diseases; however, pan-BET inhibitors have induced significant myelosuppression and gastrointestinal toxicity, perhaps due to inhibition of both tandem bromodomains (BD) of all BET family members. However, selective inhibition of just the first BD (BD1) phenocopies pan-BET inhibitor activity in preclinical models of cancer, other diseases, and, for BRDT, in the testes for a contraceptive effect. Here, we leveraged our multibillion-molecule collection of DNA-encoded chemical libraries (DECLs) to identify BET BD1-selective inhibitors of specific chirality with high potency, stability, and good cellular activity. Our findings highlight the robustness and efficiency of the DECL platform to identify specific, potent protein binders that have promise as potential anticancer and anti-inflammatory agents and as male contraceptives.
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Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections.,Modukuri RK, Yu Z, Tan Z, Ta HM, Ucisik MN, Jin Z, Anglin JL, Sharma KL, Nyshadham P, Li F, Riehle K, Faver JC, Duong K, Nagarajan S, Simmons N, Palmer SS, Teng M, Young DW, Yi JS, Kim C, Matzuk MM Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2122506119. doi:, 10.1073/pnas.2122506119. Epub 2022 May 27. PMID:35622893<ref>PMID:35622893</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7ubo" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Kim C]]
[[Category: Kim C]]

Current revision

Crystal Structure of the first bromodomain of human BRDT in complex with the inhibitor CCD-956

PDB ID 7ubo

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