8H6D

Crystal structure of human GCN5 histone acetyltransferase domain bound with glutaryl-CoA

8H6D の概要

• エントリーDOI: 10.2210/pdb8h6d/pdb
• 関連するPDBエントリー: 8H65 8H66 8H6C
• 分子名称: Histone acetyltransferase KAT2A, glutaryl-coenzyme A (2 entities in total)
• 機能のキーワード: complex, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 161153.30

構造登録者

Li, N.,Tao, Y.J.,Guo, Y.R. (登録日: 2022-10-16, 公開日: 2023-05-03, 最終更新日: 2023-10-25)

主引用文献

Li, S.,Li, N.,He, J.,Zhou, R.,Lu, Z.,Tao, Y.J.,Guo, Y.R.,Wang, Y.
Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications.
Res, 6:0109-0109, 2023

PubMed Abstract: Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases (HATs) advance our understandings in the regulation of histone modifications. However, the molecular basis of HATs selecting acyl coenzyme A (acyl-CoA) substrates for histone modification is less known. We here report that lysine acetyltransferase 2A (KAT2A) as an illustrative instance of HATs can selectively utilize acetyl-CoA, propionyl-CoA, butyryl-CoA, and succinyl-CoA to directly deposit 18 histone acylation hallmarks in nucleosome. By analyzing the co-crystal structures of the catalytic domain of KAT2A in complex with acetyl-CoA, propionyl-CoA, butyryl-CoA, malonyl-CoA, succinyl-CoA, and glutaryl-CoA, we conclude that the alternative substrate-binding pocket of KAT2A and the length and electrostatic features of the acyl chain cooperatively determine the selection of the acyl-CoA substrates by KAT2A. This study reveals the molecular basis underlying the pluripotency of HATs that selectively install acylation hallmarks in nucleosomes, which might serve as instrumental mechanism to precisely regulate histone acylation profiles in cells.

PubMed: 37040526
DOI: 10.34133/research.0109

実験手法

X-RAY DIFFRACTION (3.26 Å)