6fkp: Difference between revisions
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==Crystal structure of BAZ2A PHD zinc finger in complex with H3 10-mer AA mutant peptide== | ==Crystal structure of BAZ2A PHD zinc finger in complex with H3 10-mer AA mutant peptide== | ||
<StructureSection load='6fkp' size='340' side='right' caption='[[6fkp]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='6fkp' size='340' side='right'caption='[[6fkp]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6fkp]] is a 7 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6fkp]] is a 7 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=6FKP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FKP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fkp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fkp OCA], [https://pdbe.org/6fkp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fkp RCSB], [https://www.ebi.ac.uk/pdbsum/6fkp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fkp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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 == | ||
| Line 19: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 6fkp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6fkp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Bromodomain adjacent to zinc finger 3D structures|Bromodomain adjacent to zinc finger 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Amato | [[Category: Large Structures]] | ||
[[Category: Bortoluzzi | [[Category: Amato A]] | ||
[[Category: Ciulli | [[Category: Bortoluzzi A]] | ||
[[Category: Lucas | [[Category: Ciulli A]] | ||
[[Category: Wright | [[Category: Lucas X]] | ||
[[Category: Wright D]] | |||
Latest revision as of 15:29, 9 May 2024
Crystal structure of BAZ2A PHD zinc finger in complex with H3 10-mer AA mutant peptideCrystal structure of BAZ2A PHD zinc finger in complex with H3 10-mer AA mutant peptide
Structural highlights
FunctionBAZ2A_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 PubMedPlant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers. Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach.,Amato A, Lucas X, Bortoluzzi A, Wright D, Ciulli A ACS Chem Biol. 2018 Mar 20. doi: 10.1021/acschembio.7b01093. PMID:29529862[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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