7uuu
From Proteopedia
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==First bromodomain of BRDT liganded with compound 2c== | ==First bromodomain of BRDT liganded with compound 2c== | ||
| - | <StructureSection load='7uuu' size='340' side='right'caption='[[7uuu]]' scene=''> | + | <StructureSection load='7uuu' size='340' side='right'caption='[[7uuu]], [[Resolution|resolution]] 1.52Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UUU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7uuu]] is a 1 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=7UUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UUU FirstGlance]. <br> |
| - | </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=7uuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uuu OCA], [https://pdbe.org/7uuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uuu RCSB], [https://www.ebi.ac.uk/pdbsum/7uuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uuu ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.52Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OFR:prop-2-en-1-yl+(5S)-1-ethyl-7-methyl-5-(4-methylphenyl)-2,4-dioxo-1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimidine-6-carboxylate'>OFR</scene></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=7uuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uuu OCA], [https://pdbe.org/7uuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uuu RCSB], [https://www.ebi.ac.uk/pdbsum/7uuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uuu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Based on a previously reported 1,4-dihydropyridinebutyrolactone virtual screening hit, nine lactone ring-opened ester and seven amide analogs were prepared. The analogs were designed to provide interactions with residues at the entrance of the ZA loop of the testis-specific bromodomain (ZA) channel to enhance the affinity and selectivity for the bromodomain and extra-terminal (BET) subfamily of bromodomains. Compound testing by AlphaScreen showed that neither the affinity nor the selectivity of the ester and lactam analogs was improved for BRD4-1 and the first bromodomain of the testis-specific bromodomain (BRDT-1). The esters retained affinity comparable to the parent compound, whereas the affinity for the amide analogs was reduced 10-fold. A representative benzyl ester analog was found to retain high selectivity for BET bromodomains as shown by a BROMOscan. X-ray analysis of the allyl ester analog in complex with BRD4-1 and BRDT-1 revealed that the ester side chain is located next to the ZA loop and solvent exposed. | ||
| + | |||
| + | 1,4-Dihydropyridinebutyrolactone-derived ring-opened ester and amide analogs targeting BET bromodomains.,Jiang J, Zhao PL, Sigua LH, Chan A, Schonbrunn E, Qi J, Georg GI Arch Pharm (Weinheim). 2022 Aug 8:e2200288. doi: 10.1002/ardp.202200288. PMID:35941525<ref>PMID:35941525</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7uuu" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chan A]] | [[Category: Chan A]] | ||
[[Category: Schonbrunn E]] | [[Category: Schonbrunn E]] | ||
Current revision
First bromodomain of BRDT liganded with compound 2c
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