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==Bromodomain from Plasmodium Faciparum Gcn5, complexed with compound== | ==Bromodomain from Plasmodium Faciparum Gcn5, complexed with compound== | ||
<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 with sequence from [ | <table><tr><td colspan='2'>[[5tpx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. 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 [https://proteopedia.org/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><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tpx OCA], [https://pdbe.org/5tpx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tpx RCSB], [https://www.ebi.ac.uk/pdbsum/5tpx PDBsum], [https://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'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8IB67_PLAF7 Q8IB67_PLAF7] | |||
<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 5tpx" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5tpx" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium falciparum 3D7]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith CH]] | ||
[[Category: BRENNAN | [[Category: BRENNAN PE]] | ||
[[Category: Bountra | [[Category: Bountra C]] | ||
[[Category: DIXON | [[Category: DIXON DJ]] | ||
[[Category: Edwards | [[Category: Edwards AM]] | ||
[[Category: Hou | [[Category: Hou CFD]] | ||
[[Category: Hui | [[Category: Hui R]] | ||
[[Category: Lin | [[Category: Lin YH]] | ||
[[Category: Loppnau | [[Category: Loppnau P]] | ||
[[Category: MOUSTAKIM | [[Category: MOUSTAKIM M]] | ||
[[Category: Tempel W]] | |||
[[Category: Tempel | [[Category: Walker JR]] | ||
[[Category: Walker | |||
Latest revision as of 16:07, 4 October 2023
Bromodomain from Plasmodium Faciparum Gcn5, complexed with compoundBromodomain from Plasmodium Faciparum Gcn5, complexed with compound
Structural highlights
FunctionPublication 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. See AlsoReferences
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