1wum: Difference between revisions

Revision as of 19:07, 10 September 2015

Complex structure of PCAF bromodomain with small chemical ligand NP2

Structural highlights

1wum is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	NP2
Related:	1b91, 1jm4, 1wug
Activity:	Histone acetyltransferase, with EC number 2.3.1.48
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Development of drug resistance from mutations in the targeted viral proteins leads to continuation of viral production by chronically infected cells, contributing to HIV-mediated immune dysfunction. Targeting a host cell protein essential for viral reproduction, rather than a viral protein, may minimize the viral drug resistance problem as observed with HIV protease inhibitors. We report here the development of a novel class of N1-aryl-propane-1,3-diamine compounds using a structure-based approach that selectively inhibit the activity of the bromodomain of the human transcriptional co-activator PCAF, of which association with the HIV trans-activator Tat is essential for transcription and replication of the integrated HIV provirus.

Selective small molecules blocking HIV-1 Tat and coactivator PCAF association.,Zeng L, Li J, Muller M, Yan S, Mujtaba S, Pan C, Wang Z, Zhou MM J Am Chem Soc. 2005 Mar 2;127(8):2376-7. PMID:15724976^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996 Jul 25;382(6589):319-24. PMID:8684459 doi:10.1038/382319a0
↑ Zhang W, Bieker JJ. Acetylation and modulation of erythroid Kruppel-like factor (EKLF) activity by interaction with histone acetyltransferases. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9855-60. PMID:9707565
↑ Martinez-Balbas MA, Bauer UM, Nielsen SJ, Brehm A, Kouzarides T. Regulation of E2F1 activity by acetylation. EMBO J. 2000 Feb 15;19(4):662-71. PMID:10675335 doi:10.1093/emboj/19.4.662
↑ Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, Xiong Y, Lei QY. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013 Aug 22;51(4):506-18. doi: 10.1016/j.molcel.2013.07.002. Epub 2013 , Aug 8. PMID:23932781 doi:https://dx.doi.org/10.1016/j.molcel.2013.07.002
↑ Zeng L, Li J, Muller M, Yan S, Mujtaba S, Pan C, Wang Z, Zhou MM. Selective small molecules blocking HIV-1 Tat and coactivator PCAF association. J Am Chem Soc. 2005 Mar 2;127(8):2376-7. PMID:15724976 doi:10.1021/ja044885g

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996 Jul 25;382(6589):319-24. PMID:8684459 doi:10.1038/382319a0

[2] Zhang W, Bieker JJ. Acetylation and modulation of erythroid Kruppel-like factor (EKLF) activity by interaction with histone acetyltransferases. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9855-60. PMID:9707565

[3] Martinez-Balbas MA, Bauer UM, Nielsen SJ, Brehm A, Kouzarides T. Regulation of E2F1 activity by acetylation. EMBO J. 2000 Feb 15;19(4):662-71. PMID:10675335 doi:10.1093/emboj/19.4.662

[4] Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, Xiong Y, Lei QY. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013 Aug 22;51(4):506-18. doi: 10.1016/j.molcel.2013.07.002. Epub 2013 , Aug 8. PMID:23932781 doi:https://dx.doi.org/10.1016/j.molcel.2013.07.002

[5] Zeng L, Li J, Muller M, Yan S, Mujtaba S, Pan C, Wang Z, Zhou MM. Selective small molecules blocking HIV-1 Tat and coactivator PCAF association. J Am Chem Soc. 2005 Mar 2;127(8):2376-7. PMID:15724976 doi:10.1021/ja044885g

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[2]

[3]

[4]

[5]

@@ Line 2: / Line 2: @@
 <StructureSection load='1wum' size='340' side='right' caption='[[1wum]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1wum]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WUM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1wum]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WUM FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NP2:N-(3-AMINOPROPYL)-2-NITROBENZENAMINE'>NP2</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b91|1b91]], [[1jm4|1jm4]], [[1wug|1wug]]</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=1wum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wum OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wum RCSB], [http://www.ebi.ac.uk/pdbsum/1wum PDBsum]</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=1wum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wum OCA], [http://pdbe.org/1wum PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wum RCSB], [http://www.ebi.ac.uk/pdbsum/1wum PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PCAF_HUMAN PCAF_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. 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>
+[[http://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1wum" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 </StructureSection>
 [[Category: Histone acetyltransferase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Li, J]]
 [[Category: Mujtaba, S]]

1wum: Difference between revisions

Revision as of 19:07, 10 September 2015

Complex structure of PCAF bromodomain with small chemical ligand NP2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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