3M56

SET7/9 Y305F in complex with TAF10-K189me2 peptide and AdoHcy

3M56 の概要

• エントリーDOI: 10.2210/pdb3m56/pdb
• 関連するPDBエントリー: 2F69 3M53 3M54 3M55 3M57 3M58 3M59 3M5A
• 分子名称: Histone-lysine N-methyltransferase SETD7, TAF10-K189me2 PEPTIDE, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• 機能のキーワード: ternary complex, set domain, methyltransferase, s-adenosyl-l-homocysteine, taf10 peptide, n-dimethyllysine, chromatin regulator, chromosomal protein, s-adenosyl-l-methionine, transcription, transcription regulation, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q8WTS6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30694.26

構造登録者

Del Rizzo, P.A.,Couture, J.-F.,Roiko, M.S.,Strunk, B.S.,Brunzelle, J.S.,Dirk, L.M.,Houtz, R.L.,Trievel, R.C. (登録日: 2010-03-12, 公開日: 2010-07-28, 最終更新日: 2023-09-06)

主引用文献

Del Rizzo, P.A.,Couture, J.F.,Dirk, L.M.,Strunk, B.S.,Roiko, M.S.,Brunzelle, J.S.,Houtz, R.L.,Trievel, R.C.
SET7/9 catalytic mutants reveal the role of active site water molecules in lysine multiple methylation.
J.Biol.Chem., 285:31849-31858, 2010

PubMed Abstract: SET domain lysine methyltransferases (KMTs) methylate specific lysine residues in histone and non-histone substrates. These enzymes also display product specificity by catalyzing distinct degrees of methylation of the lysine ε-amino group. To elucidate the molecular mechanism underlying this specificity, we have characterized the Y245A and Y305F mutants of the human KMT SET7/9 (also known as KMT7) that alter its product specificity from a monomethyltransferase to a di- and a trimethyltransferase, respectively. Crystal structures of these mutants in complex with peptides bearing unmodified, mono-, di-, and trimethylated lysines illustrate the roles of active site water molecules in aligning the lysine ε-amino group for methyl transfer with S-adenosylmethionine. Displacement or dissociation of these solvent molecules enlarges the diameter of the active site, accommodating the increasing size of the methylated ε-amino group during successive methyl transfer reactions. Together, these results furnish new insights into the roles of active site water molecules in modulating lysine multiple methylation by SET domain KMTs and provide the first molecular snapshots of the mono-, di-, and trimethyl transfer reactions catalyzed by these enzymes.

PubMed: 20675860
DOI: 10.1074/jbc.M110.114587

実験手法

X-RAY DIFFRACTION (1.65 Å)