6fi0
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6fi0 is ON HOLD until Paper Publication Authors: Amato, A., Lucas, X., Bortoluzzi, A., Wright, D., Ciulli, A. Description: Crystal structure of BAZ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of BAZ2A PHD zinc finger in complex with Fr 19== | |
| + | <StructureSection load='6fi0' size='340' side='right' caption='[[6fi0]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6fi0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FI0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FI0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DEW:2-azanyl-1-(6,7-dihydro-4~{H}-thieno[3,2-c]pyridin-5-yl)ethanone'>DEW</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAZ2A, KIAA0314, TIP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6fi0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fi0 OCA], [http://pdbe.org/6fi0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fi0 RCSB], [http://www.ebi.ac.uk/pdbsum/6fi0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fi0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Plant 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<ref>PMID:29529862</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 6fi0" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Amato, A]] | ||
[[Category: Bortoluzzi, A]] | [[Category: Bortoluzzi, A]] | ||
| + | [[Category: Ciulli, A]] | ||
[[Category: Lucas, X]] | [[Category: Lucas, X]] | ||
| - | [[Category: | + | [[Category: Wright, D]] |
| + | [[Category: Baz2a]] | ||
| + | [[Category: Bromodomain]] | ||
| + | [[Category: Epigenetic]] | ||
| + | [[Category: Fr 19]] | ||
| + | [[Category: Fr19]] | ||
| + | [[Category: Fragment]] | ||
| + | [[Category: Ligandability]] | ||
| + | [[Category: Phd zinc finger]] | ||
| + | [[Category: Transcription]] | ||
Current revision
Crystal structure of BAZ2A PHD zinc finger in complex with Fr 19
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Categories: Human | Amato, A | Bortoluzzi, A | Ciulli, A | Lucas, X | Wright, D | Baz2a | Bromodomain | Epigenetic | Fr 19 | Fr19 | Fragment | Ligandability | Phd zinc finger | Transcription
