5mkz
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
==N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH 4-chloro-2-methyl-5-(((3-methylthiophen-2-yl)methyl)amino)pyridazin-3(2H)-one== | ==N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH 4-chloro-2-methyl-5-(((3-methylthiophen-2-yl)methyl)amino)pyridazin-3(2H)-one== | ||
| - | <StructureSection load='5mkz' size='340' side='right' caption='[[5mkz]], [[Resolution|resolution]] 1.62Å' scene=''> | + | <StructureSection load='5mkz' size='340' side='right'caption='[[5mkz]], [[Resolution|resolution]] 1.62Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5mkz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MKZ OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5mkz]] 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=5MKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MKZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RNK:4-chloranyl-2-methyl-5-[(3-methylthiophen-2-yl)methylamino]pyridazin-3-one'>RNK</scene></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]] 1.62Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RNK:4-chloranyl-2-methyl-5-[(3-methylthiophen-2-yl)methylamino]pyridazin-3-one'>RNK</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=5mkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mkz OCA], [https://pdbe.org/5mkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mkz RCSB], [https://www.ebi.ac.uk/pdbsum/5mkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mkz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [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 == | ||
| - | [ | + | [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 == | ||
| + | p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and >/=18000-fold selectivity over the BET family, together with >/=70-fold selectivity over the wider bromodomain families. | ||
| + | |||
| + | Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe.,Humphreys PG, Bamborough P, Chung CW, Craggs PD, Gordon L, Grandi P, Hayhow TG, Hussain J, Jones KL, Lindon M, Michon AM, Renaux JF, Suckling CJ, Tough DF, Prinjha RK J Med Chem. 2017 Jan 26;60(2):695-709. doi: 10.1021/acs.jmedchem.6b01566. Epub, 2017 Jan 9. PMID:28002667<ref>PMID:28002667</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5mkz" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Chung C-W]] |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH 4-chloro-2-methyl-5-(((3-methylthiophen-2-yl)methyl)amino)pyridazin-3(2H)-one
| |||||||||||
