6at0 | pdb_00006at0

Chromodomain HP1 with a p-nitro-L-phenylalanine mutation at position 24 bound to histone H3 peptide containing trimethyl lysine

spinqualitylabelsall models 6at0, resolution 1.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6at0 is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.285Å Ligands: M3L, PPN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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