5o4s: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the human BRPF1 bromodomain in complex with BZ135== | ==Crystal structure of the human BRPF1 bromodomain in complex with BZ135== | ||
<StructureSection load='5o4s' size='340' side='right' caption='[[5o4s]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='5o4s' size='340' side='right'caption='[[5o4s]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5o4s]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5o4s]] 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=5O4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O4S FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9KW:~{N}-[1,4-dimethyl-7-morpholin-4-yl-2,3-bis(oxidanylidene)quinoxalin-6-yl]-5,6,7,8-tetrahydronaphthalene-2-sulfonamide'>9KW</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9KW:~{N}-[1,4-dimethyl-7-morpholin-4-yl-2,3-bis(oxidanylidene)quinoxalin-6-yl]-5,6,7,8-tetrahydronaphthalene-2-sulfonamide'>9KW</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5o4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o4s OCA], [https://pdbe.org/5o4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o4s RCSB], [https://www.ebi.ac.uk/pdbsum/5o4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o4s ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/BRPF1_HUMAN BRPF1_HUMAN] Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. Positively regulates the transcription of RUNX1 and RUNX2.<ref>PMID:16387653</ref> <ref>PMID:18794358</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 19: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5o4s" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5o4s" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Peregrin|Peregrin]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Caflisch A]] | ||
[[Category: | [[Category: Zhu J]] | ||
Latest revision as of 22:08, 29 November 2023
Crystal structure of the human BRPF1 bromodomain in complex with BZ135Crystal structure of the human BRPF1 bromodomain in complex with BZ135
Structural highlights
FunctionBRPF1_HUMAN Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. Positively regulates the transcription of RUNX1 and RUNX2.[1] [2] Publication Abstract from PubMedBromodomain and plant homeodomain (PHD) finger containing protein 1 (BRPF1) is a member of subfamily IV of the human bromodomains. Experimental evidence suggests that BRPF1 is involved in leukemia. In a previous high-throughput docking campaign we identified several chemotypes targeting the BRPF1 bromodomain. Here, pharmacophore searches using the binding modes of two of these chemotypes resulted in two new series of ligands of the BRPF1 bromodomain. The 2,3-dioxo-quinoxaline 21 exhibits a 2-muM affinity for the BRPF1 bromodomain in two different competition binding assays, and more than 100-fold selectivity for BRPF1 against other members of subfamily IV and representatives of other subfamilies. Cellular activity is confirmed by a viability assay in a leukemia cell line. Isothermal titration calorimetry measurements reveal enthalpy-driven binding for compounds 21, 26 (KD=3muM), and the 2,4-dimethyl-oxazole derivative 42 (KD=10muM). Multiple molecular dynamics simulations and a dozen co-crystal structures at high resolution provide useful information for further optimization of affinity for the BRPF1 bromodomain. Structure-based discovery of selective BRPF1 bromodomain inhibitors.,Zhu J, Zhou C, Caflisch A Eur J Med Chem. 2018 Jun 2;155:337-352. doi: 10.1016/j.ejmech.2018.05.037. PMID:29902720[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||