5fe6: Difference between revisions
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==Crystal structure of human PCAF bromodomain in complex with fragment ZB1916 (fragment 10)== | |||
<StructureSection load='5fe6' size='340' side='right'caption='[[5fe6]], [[Resolution|resolution]] 1.77Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5fe6]] 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=5FE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FE6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5WZ:(4-AZANYLPIPERIDIN-1-YL)-CYCLOPROPYL-METHANONE'>5WZ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5fe6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fe6 OCA], [https://pdbe.org/5fe6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fe6 RCSB], [https://www.ebi.ac.uk/pdbsum/5fe6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fe6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KAT2B_HUMAN KAT2B_HUMAN] 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. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.<ref>PMID:8684459</ref> <ref>PMID:9707565</ref> <ref>PMID:10675335</ref> <ref>PMID:23932781</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The P300/CBP-associated factor plays a central role in retroviral infection and cancer development, and the C-terminal bromodomain provides an opportunity for selective targeting. Here, we report several new classes of acetyl-lysine mimetic ligands ranging from mM to low micromolar affinity that were identified using fragment screening approaches. The binding modes of the most attractive fragments were determined using high resolution crystal structures providing chemical starting points and structural models for the development of potent and selective PCAF inhibitors. | |||
Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain.,Chaikuad A, Lang S, Brennan PE, Temperini C, Fedorov O, Hollander J, Nachane R, Abell C, Muller S, Siegal G, Knapp S J Med Chem. 2016 Feb 25;59(4):1648-53. doi: 10.1021/acs.jmedchem.5b01719. Epub, 2016 Jan 13. PMID:26731131<ref>PMID:26731131</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5fe6" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Bountra | ==See Also== | ||
[[Category: | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Arrowsmith CH]] | |||
[[Category: Bountra C]] | |||
[[Category: Chaikuad A]] | |||
[[Category: Edwards AM]] | |||
[[Category: Knapp S]] | |||
[[Category: Von Delft F]] | |||
Latest revision as of 09:47, 19 July 2023
Crystal structure of human PCAF bromodomain in complex with fragment ZB1916 (fragment 10)Crystal structure of human PCAF bromodomain in complex with fragment ZB1916 (fragment 10)
Structural highlights
FunctionKAT2B_HUMAN 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. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.[1] [2] [3] [4] Publication Abstract from PubMedThe P300/CBP-associated factor plays a central role in retroviral infection and cancer development, and the C-terminal bromodomain provides an opportunity for selective targeting. Here, we report several new classes of acetyl-lysine mimetic ligands ranging from mM to low micromolar affinity that were identified using fragment screening approaches. The binding modes of the most attractive fragments were determined using high resolution crystal structures providing chemical starting points and structural models for the development of potent and selective PCAF inhibitors. Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain.,Chaikuad A, Lang S, Brennan PE, Temperini C, Fedorov O, Hollander J, Nachane R, Abell C, Muller S, Siegal G, Knapp S J Med Chem. 2016 Feb 25;59(4):1648-53. doi: 10.1021/acs.jmedchem.5b01719. Epub, 2016 Jan 13. PMID:26731131[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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