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| | ==Crystal structure of the bromodomain of human GCN5, the general control of amino-acid synthesis protein 5-like 2== | | ==Crystal structure of the bromodomain of human GCN5, the general control of amino-acid synthesis protein 5-like 2== |
| - | <StructureSection load='3d7c' size='340' side='right' caption='[[3d7c]], [[Resolution|resolution]] 2.06Å' scene=''> | + | <StructureSection load='3d7c' size='340' side='right'caption='[[3d7c]], [[Resolution|resolution]] 2.06Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3d7c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3D7C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3d7c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D7C FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GCN5L2, GCN5, HGCN5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GCN5L2, GCN5, HGCN5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3d7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d7c OCA], [http://pdbe.org/3d7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3d7c RCSB], [http://www.ebi.ac.uk/pdbsum/3d7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3d7c ProSAT]</span></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=3d7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d7c OCA], [https://pdbe.org/3d7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d7c RCSB], [https://www.ebi.ac.uk/pdbsum/3d7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d7c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KAT2A_HUMAN KAT2A_HUMAN]] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles. Also acetylates non-histone proteins, such as CEBPB (PubMed:17301242). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. 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:17301242</ref> <ref>PMID:19103755</ref> | + | [[https://www.uniprot.org/uniprot/KAT2A_HUMAN KAT2A_HUMAN]] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles. Also acetylates non-histone proteins, such as CEBPB (PubMed:17301242). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. 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:17301242</ref> <ref>PMID:19103755</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Histone acetyltransferase|Histone acetyltransferase]] | + | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Arrowsmith, C H]] | | [[Category: Arrowsmith, C H]] |
| | [[Category: Bountra, C]] | | [[Category: Bountra, C]] |
| Structural highlights
Function
[KAT2A_HUMAN] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles. Also acetylates non-histone proteins, such as CEBPB (PubMed:17301242). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. 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]
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
Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.
Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wiper-Bergeron N, Salem HA, Tomlinson JJ, Wu D, Hache RJ. Glucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPbeta by GCN5. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2703-8. Epub 2007 Feb 14. PMID:17301242 doi:http://dx.doi.org/10.1073/pnas.0607378104
- ↑ Guelman S, Kozuka K, Mao Y, Pham V, Solloway MJ, Wang J, Wu J, Lill JR, Zha J. The double-histone-acetyltransferase complex ATAC is essential for mammalian development. Mol Cell Biol. 2009 Mar;29(5):1176-88. doi: 10.1128/MCB.01599-08. Epub 2008 Dec, 22. PMID:19103755 doi:10.1128/MCB.01599-08
- ↑ Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell. 2012 Mar 30;149(1):214-31. PMID:22464331 doi:10.1016/j.cell.2012.02.013
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