View source for 6asz


==Chromodomain HP1 with Y24F mutation bound to histone H3 peptide containing trimethyl lysine==
<StructureSection load='6asz' size='340' side='right'caption='[[6asz]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6asz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5kog 5kog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ASZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ASZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.518&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</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=6asz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6asz OCA], [https://pdbe.org/6asz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6asz RCSB], [https://www.ebi.ac.uk/pdbsum/6asz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6asz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HP1_DROME HP1_DROME] Structural component of heterochromatin, involved in gene repression and the modification of position-effect-variegation. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trimethyllysine (Kme3) reader proteins are targets for inhibition due to their role in mediating gene expression. Although all such reader proteins bind Kme3 in an aromatic cage, the driving force for binding may differ; some readers exhibit evidence for cation-pi interactions whereas others do not. We report a general unnatural amino acid mutagenesis approach to quantify the contribution of individual tyrosines to cation binding using the HP1 chromodomain as a model system. We demonstrate that two tyrosines (Y24 and Y48) bind to a Kme3-histone tail peptide via cation-pi interactions, but linear free energy trends suggest they do not contribute equally to binding. X-ray structures and computational analysis suggest that the distance and degree of contact between Tyr residues and Kme3 plays an important role in tuning cation-pi-mediated Kme3 recognition. Although cation-pi interactions have been studied in a number of proteins, this work is the first to utilize direct binding assays, X-ray crystallography, and modeling, to pinpoint factors that influence the magnitude of the individual cation-pi interactions.

Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis.,Baril SA, Koenig AL, Krone MW, Albanese KI, He CQ, Lee GY, Houk KN, Waters ML, Brustad EM J Am Chem Soc. 2017 Nov 20. doi: 10.1021/jacs.7b09223. PMID:29111699<ref>PMID:29111699</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6asz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Baril SA]]
[[Category: Brustad EM]]
[[Category: Waters ML]]