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| | <StructureSection load='5or8' size='340' side='right'caption='[[5or8]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5or8' size='340' side='right'caption='[[5or8]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5or8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OR8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OR8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5or8]] 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=5OR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OR8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JR4:~{N}-[(4-fluorophenyl)methyl]-1,3,6-trimethyl-2-oxidanylidene-benzimidazole-5-sulfonamide'>JR4</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]] 2.4Å</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=5or8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5or8 OCA], [http://pdbe.org/5or8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5or8 RCSB], [http://www.ebi.ac.uk/pdbsum/5or8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5or8 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JR4:~{N}-[(4-fluorophenyl)methyl]-1,3,6-trimethyl-2-oxidanylidene-benzimidazole-5-sulfonamide'>JR4</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=5or8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5or8 OCA], [https://pdbe.org/5or8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5or8 RCSB], [https://www.ebi.ac.uk/pdbsum/5or8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5or8 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: Dalle Vedove A]] |
| - | [[Category: Marchand, J R]]
| + | [[Category: Lolli G]] |
| - | [[Category: Vedove, A Dalle]]
| + | [[Category: Marchand J-R]] |
| - | [[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 high-throughput docking protocol called ALTA-VS (anchor-based library tailoring virtual screening) was developed in 2005 for the efficient in silico screening of large libraries of compounds by pre-selection of only those molecules that have optimal fragments (anchors) for the protein target. Here we present an updated version of ALTA-VS with a broader range of potential applications. The evaluation of binding energy makes use of a classical force field with implicit solvent in the continuum dielectric approximation. In about two days per protein target on a 96-core compute cluster (equipped with Xeon E3-1280 quad core processors at 2.5 GHz), the screening of a library of nearly 77 000 diverse molecules with the updated ALTA-VS protocol has resulted in the identification of 19, 3, 3, and 2 micromolar inhibitors of the human bromodomains ATAD2, BAZ2B, BRD4(1), and CREBBP, respectively. The success ratio (i.e., number of actives in a competition binding assay in vitro divided by the number of compounds tested) ranges from 8% to 13% in dose-response measurements. The poses predicted by fragment-based docking for the three ligands of the BAZ2B bromodomain were confirmed by protein X-ray crystallography.
Discovery of Inhibitors of Four Bromodomains by Fragment-Anchored Ligand Docking.,Marchand JR, Vedove AD, Lolli G, Caflisch A J Chem Inf Model. 2017 Sep 1. doi: 10.1021/acs.jcim.7b00336. PMID:28862840[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Marchand JR, Vedove AD, Lolli G, Caflisch A. Discovery of Inhibitors of Four Bromodomains by Fragment-Anchored Ligand Docking. J Chem Inf Model. 2017 Sep 1. doi: 10.1021/acs.jcim.7b00336. PMID:28862840 doi:http://dx.doi.org/10.1021/acs.jcim.7b00336
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