5EG2

SET7/9 N265A in complex with AdoHcy and TAF10 peptide

5EG2 の概要

• エントリーDOI: 10.2210/pdb5eg2/pdb
• 分子名称: Histone-lysine N-methyltransferase SETD7, Transcription initiation factor TFIID subunit 10, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• 機能のキーワード: transferase-transcription factor complex, transferase/transcription factor
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30737.23

構造登録者

Kroner, G.M.,Fick, R.J.,Trievel, R.C. (登録日: 2015-10-26, 公開日: 2016-01-13, 最終更新日: 2023-09-27)

主引用文献

Fick, R.J.,Kroner, G.M.,Nepal, B.,Magnani, R.,Horowitz, S.,Houtz, R.L.,Scheiner, S.,Trievel, R.C.
Sulfur-Oxygen Chalcogen Bonding Mediates AdoMet Recognition in the Lysine Methyltransferase SET7/9.
Acs Chem.Biol., 11:748-754, 2016

PubMed Abstract: Recent studies have demonstrated that carbon-oxygen (CH···O) hydrogen bonds have important roles in S-adenosylmethionine (AdoMet) recognition and catalysis in methyltransferases. Here, we investigate noncovalent interactions that occur between the AdoMet sulfur cation and oxygen atoms in methyltransferase active sites. These interactions represent sulfur-oxygen (S···O) chalcogen bonds in which the oxygen atom donates a lone pair of electrons to the σ antibonding orbital of the AdoMet sulfur atom. Structural, biochemical, and computational analyses of an asparagine mutation in the lysine methyltransferase SET7/9 that abolishes AdoMet S···O chalcogen bonding reveal that this interaction enhances substrate binding affinity relative to the product S-adenosylhomocysteine. Corroborative quantum mechanical calculations demonstrate that sulfonium systems form strong S···O chalcogen bonds relative to their neutral thioether counterparts. An inspection of high-resolution crystal structures reveals the presence of AdoMet S···O chalcogen bonding in different classes of methyltransferases, illustrating that these interactions are not limited to SET domain methyltransferases. Together, these results demonstrate that S···O chalcogen bonds contribute to AdoMet recognition and can enable methyltransferases to distinguish between substrate and product.

PubMed: 26713889
DOI: 10.1021/acschembio.5b00852

実験手法

X-RAY DIFFRACTION (1.55 Å)