5ml0: Difference between revisions
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<StructureSection load='5ml0' size='340' side='right' caption='[[5ml0]], [[Resolution|resolution]] 1.64Å' scene=''> | <StructureSection load='5ml0' size='340' side='right' caption='[[5ml0]], [[Resolution|resolution]] 1.64Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ml0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ML0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ML0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5ml0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ML0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ML0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=P2L:4-chlorol-2-methyl-5-[[(3~{R})-1-methylpiperidin-3-yl]amino]pyridazin-3-one'>P2L</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=P2L:4-chlorol-2-methyl-5-[[(3~{R})-1-methylpiperidin-3-yl]amino]pyridazin-3-one'>P2L</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kat2b, Pcaf ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=5ml0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ml0 OCA], [http://pdbe.org/5ml0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ml0 RCSB], [http://www.ebi.ac.uk/pdbsum/5ml0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ml0 ProSAT]</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=5ml0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ml0 OCA], [http://pdbe.org/5ml0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ml0 RCSB], [http://www.ebi.ac.uk/pdbsum/5ml0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ml0 ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/KAT2B_MOUSE KAT2B_MOUSE]] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (By similarity). | [[http://www.uniprot.org/uniprot/KAT2B_MOUSE KAT2B_MOUSE]] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (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 5ml0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Histone acetyltransferase]] | [[Category: Histone acetyltransferase]] | ||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Chung, C W]] | [[Category: Chung, C W]] | ||
[[Category: Antagonist]] | [[Category: Antagonist]] | ||
Revision as of 23:40, 24 January 2018
Bromodomain of Mouse PCAF with (R)-4-chloro-2-methyl-5-((1-methylpiperidin-3-yl)amino)pyridazin-3(2H)-oneBromodomain of Mouse PCAF with (R)-4-chloro-2-methyl-5-((1-methylpiperidin-3-yl)amino)pyridazin-3(2H)-one
Structural highlights
Function[KAT2B_MOUSE] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (By similarity). Publication Abstract from PubMedp300/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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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