6ASZ

Chromodomain HP1 with Y24F mutation bound to histone H3 peptide containing trimethyl lysine

「5KOG」から置き換えられました

6ASZ の概要

• エントリーDOI: 10.2210/pdb6asz/pdb
• 分子名称: Heterochromatin protein 1, trimethyl lysine histone H3 tail peptide (3 entities in total)
• 機能のキーワード: histone reader, transcription
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9304.33

構造登録者

Brustad, E.M.,Baril, S.A.,Waters, M.L. (登録日: 2017-08-27, 公開日: 2017-12-06, 最終更新日: 2023-10-04)

主引用文献

Baril, S.A.,Koenig, A.L.,Krone, M.W.,Albanese, K.I.,He, C.Q.,Lee, G.Y.,Houk, K.N.,Waters, M.L.,Brustad, E.M.
Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis.
J. Am. Chem. Soc., 139:17253-17256, 2017

PubMed Abstract: 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-π 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-π 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-π-mediated Kme3 recognition. Although cation-π 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-π interactions.

PubMed: 29111699
DOI: 10.1021/jacs.7b09223

実験手法

X-RAY DIFFRACTION (1.518 Å)