5mgm

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(Difference between revisions)

Revision as of 07:18, 19 August 2020

Crystal Structure of BAZ2A bromodomain in complex with acetophenone derivative 4

Structural highlights

5mgm is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5mgj, 5mgk, 5mgl
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 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.

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

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/5mgm"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of BAZ2A bromodomain in complex with acetophenone derivative 4==
-<StructureSection load='5mgm' size='340' side='right' caption='[[5mgm]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='5mgm' size='340' side='right'caption='[[5mgm]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mgm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MGM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mgm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MGM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7MZ:1-(3-PYRIMIDIN-2-YLOXYPHENYL)ETHANONE'>7MZ</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7MZ:1-(3-PYRIMIDIN-2-YLOXYPHENYL)ETHANONE'>7MZ</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5mgj|5mgj]], [[5mgk|5mgk]], [[5mgl|5mgl]]</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=5mgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgm OCA], [http://pdbe.org/5mgm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgm RCSB], [http://www.ebi.ac.uk/pdbsum/5mgm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgm 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=5mgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgm OCA], [http://pdbe.org/5mgm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgm RCSB], [http://www.ebi.ac.uk/pdbsum/5mgm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgm ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5mgm" 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]]

5mgm

From Proteopedia

Revision as of 07:18, 19 August 2020

Crystal Structure of BAZ2A bromodomain in complex with acetophenone derivative 4

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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