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5or8

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Revision as of 07:30, 2 September 2020

Crystal Structure of BAZ2A bromodomain in complex with 1,3-dimethyl-benzimidazolone compound 1

Structural highlights

5or8 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5or8"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of BAZ2A bromodomain in complex with 1,3-dimethyl-benzimidazolone compound 1==
-<StructureSection load='5or8' size='340' side='right' caption='[[5or8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5or8' size='340' side='right'caption='[[5or8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OR8 FirstGlance]. <br>
+<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>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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'>[http://oca.weizmann.ac.il/oca-docs/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='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>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 5or8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain adjacent to zinc finger 3D structures|Bromodomain adjacent to zinc finger 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Caflisch, A]]
 [[Category: Lolli, G]]

5or8

From Proteopedia

Revision as of 07:30, 2 September 2020

Crystal Structure of BAZ2A bromodomain in complex with 1,3-dimethyl-benzimidazolone compound 1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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