5tpx: Difference between revisions
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<StructureSection load='5tpx' size='340' side='right' caption='[[5tpx]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='5tpx' size='340' side='right' caption='[[5tpx]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5tpx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TPX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TPX FirstGlance]. <br> | <table><tr><td colspan='2'>[[5tpx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TPX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TPX FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7H7:(1S,2S)-N~1~,N~1~-DIMETHYL-N~2~-(3-METHYL[1,2,4]TRIAZOLO[3,4-A]PHTHALAZIN-6-YL)-1-PHENYLPROPANE-1,2-DIAMINE'>7H7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7H7:(1S,2S)-N~1~,N~1~-DIMETHYL-N~2~-(3-METHYL[1,2,4]TRIAZOLO[3,4-A]PHTHALAZIN-6-YL)-1-PHENYLPROPANE-1,2-DIAMINE'>7H7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qns|4qns]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qns|4qns]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF3D7_0823300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=5tpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tpx OCA], [http://pdbe.org/5tpx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tpx RCSB], [http://www.ebi.ac.uk/pdbsum/5tpx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tpx 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=5tpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tpx OCA], [http://pdbe.org/5tpx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tpx RCSB], [http://www.ebi.ac.uk/pdbsum/5tpx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tpx ProSAT]</span></td></tr> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Histone acetyltransferase]] | [[Category: Histone acetyltransferase]] | ||
[[Category: Plaf7]] | |||
[[Category: Arrowsmith, C H]] | [[Category: Arrowsmith, C H]] | ||
[[Category: BRENNAN, P E]] | [[Category: BRENNAN, P E]] | ||
Revision as of 13:18, 22 November 2017
Bromodomain from Plasmodium Faciparum Gcn5, complexed with compoundBromodomain from Plasmodium Faciparum Gcn5, complexed with compound
Structural highlights
Publication Abstract from PubMedThe p300/CBP-associated factor (PCAF) and related GCN5 bromodomain-containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine-based L-45 (dubbed L-Moses) as the first potent, selective, and cell-active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)-(-)-norephedrine furnished L-45 in enantiopure form. L-45 was shown to disrupt PCAF-Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co-crystal structure of L-45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L-45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell-permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use. Discovery of a PCAF Bromodomain Chemical Probe.,Moustakim M, Clark PG, Trulli L, Fuentes de Arriba AL, Ehebauer MT, Chaikuad A, Murphy EJ, Mendez-Johnson J, Daniels D, Hou CD, Lin YH, Walker JR, Hui R, Yang H, Dorrell L, Rogers CM, Monteiro OP, Fedorov O, Huber KV, Knapp S, Heer J, Dixon DJ, Brennan PE Angew Chem Int Ed Engl. 2016 Dec 14. doi: 10.1002/anie.201610816. PMID:27966810[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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