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| | <StructureSection load='5mgk' size='340' side='right'caption='[[5mgk]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='5mgk' size='340' side='right'caption='[[5mgk]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mgk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MGK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mgk]] is a 1 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=5MGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MGK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7MW:METHYL+4-PROPANOYL-1~{H}-PYRROLE-2-CARBOXYLATE'>7MW</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.301Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5mgf|5mgf]], [[5mgj|5mgj]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7MW:METHYL+4-PROPANOYL-1~{H}-PYRROLE-2-CARBOXYLATE'>7MW</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgk OCA], [http://pdbe.org/5mgk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgk RCSB], [http://www.ebi.ac.uk/pdbsum/5mgk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgk 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=5mgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgk OCA], [https://pdbe.org/5mgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgk RCSB], [https://www.ebi.ac.uk/pdbsum/5mgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgk ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BAZ2A_HUMAN BAZ2A_HUMAN]] Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity). | + | [https://www.uniprot.org/uniprot/BAZ2A_HUMAN BAZ2A_HUMAN] Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Caflisch, A]] | + | [[Category: Caflisch A]] |
| - | [[Category: Lolli, G]] | + | [[Category: Lolli G]] |
| - | [[Category: Spiliotopoulos, D]] | + | [[Category: Spiliotopoulos D]] |
| - | [[Category: Four helical bundle]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
BAZ2A_HUMAN Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity).
Publication Abstract from PubMed
The bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) is implicated in aggressive prostate cancer. The BAZ2A bromodomain is a challenging target because of the shallow pocket of its natural ligand, the acetylated side chain of lysine. Here, we report the successful screening of a library of nearly 1500 small molecules by high-throughput docking and force field-based binding-energy evaluation. For seven of the 20 molecules selected in silico, evidence of binding to the BAZ2A bromodomain is provided by ligand-observed NMR spectroscopy. Two of these compounds show a favorable ligand efficiency of 0.42 kcal/mol per non-hydrogen atom in a competition-binding assay. The crystal structures of the BAZ2A bromodomain in complex with four fragment hits validate the predicted binding modes. The binding modes of compounds 1 and 3 are compatible with ligand growing for optimization of affinity for BAZ2A and selectivity against the close homologue BAZ2B.
Discovery of BAZ2A bromodomain ligands.,Spiliotopoulos D, Wamhoff EC, Lolli G, Rademacher C, Caflisch A Eur J Med Chem. 2017 Aug 12;139:564-572. doi: 10.1016/j.ejmech.2017.08.028. PMID:28837921[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Spiliotopoulos D, Wamhoff EC, Lolli G, Rademacher C, Caflisch A. Discovery of BAZ2A bromodomain ligands. Eur J Med Chem. 2017 Aug 12;139:564-572. doi: 10.1016/j.ejmech.2017.08.028. PMID:28837921 doi:http://dx.doi.org/10.1016/j.ejmech.2017.08.028
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