|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Solution NMR structures of BRD4 ET domain in complex with NSD3_1 peptide== | | ==Solution NMR structures of BRD4 ET domain in complex with NSD3_1 peptide== |
| - | <StructureSection load='2ncz' size='340' side='right' caption='[[2ncz]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2ncz' size='340' side='right'caption='[[2ncz]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ncz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NCZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NCZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ncz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NCZ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2nd0|2nd0]], [[2nd1|2nd1]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=2ncz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ncz OCA], [https://pdbe.org/2ncz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ncz RCSB], [https://www.ebi.ac.uk/pdbsum/2ncz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ncz ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=2ncz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ncz OCA], [http://pdbe.org/2ncz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ncz RCSB], [http://www.ebi.ac.uk/pdbsum/2ncz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ncz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> [[http://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN]] Note=Defects in WHSC1L1 may be involved in non small cell lung carcinomas (NSCLC). Amplified or overexpressed in NSCLC.<ref>PMID:15983384</ref> Note=A chromosomal aberration involving WHSC1L1 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98. | + | [https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). [[http://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN]] Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.<ref>PMID:16682010</ref> | + | [https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The bromodomains and extra-terminal domain (BET) proteins direct gene transcription in chromatin, and represent new drug targets for cancer and inflammation. Here we report that the ET domain of the BET protein BRD4 recognizes an amphipathic protein sequence motif through establishing a two-strand antiparallel beta sheet anchored on a hydrophobic cleft of the three-helix bundle. This structural mechanism likely explains BRD4 interactions with numerous cellular and viral proteins such as Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen, and NSD3 whose interaction with BRD4 via this ET domain mechanism is essential for acute myeloid leukemia maintenance.
| + | |
| - | | + | |
| - | Structural Mechanism of Transcriptional Regulator NSD3 Recognition by the ET Domain of BRD4.,Zhang Q, Zeng L, Shen C, Ju Y, Konuma T, Zhao C, Vakoc CR, Zhou MM Structure. 2016 Jul 6;24(7):1201-8. doi: 10.1016/j.str.2016.04.019. Epub 2016 Jun, 9. PMID:27291650<ref>PMID:27291650</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 2ncz" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Zeng, L]] | + | [[Category: Zeng L]] |
| - | [[Category: Zhou, M]] | + | [[Category: Zhou M]] |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription-transferase complex]]
| + | |
| - | [[Category: Transferase]]
| + | |
