8H6C

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

Summary for 8H6C

• Entry DOI: 10.2210/pdb8h6c/pdb
• Related: 8H65 8H66
• Descriptor: Histone acetyltransferase KAT2A, MALONYL-COENZYME A (3 entities in total)
• Functional Keywords: complex, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 8
• Total formula weight: 160928.87

Authors

Li, N.,Tao, Y.J.,Guo, Y.R. (deposition date: 2022-10-16, release date: 2023-05-03, Last modification date: 2023-10-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)