9TZ6

Crystal structure of CREBBP-R1446H histone acetyltransferase domain in complex with CoA

Summary for 9TZ6

• Entry DOI: 10.2210/pdb9tz6/pdb
• Descriptor: histone acetyltransferase, ZINC ION, COENZYME A, ... (4 entities in total)
• Functional Keywords: histone acetyltransferase, transferase
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 1
• Total formula weight: 76062.51

Authors

Mechaly, A.E.,Zhang, W.,Haouz, A.,Green, M.,Rodrigues-Lima, F. (deposition date: 2026-01-22, release date: 2026-10-21)

Primary citation

Zhang, W.,Yang, H.,Mechaly, A.,Li, Z.,Cui, G.,Regad, L.,Duval, R.,Dairou, J.,Haouz, A.,Green, M.R.,Rodrigues Lima, F.
Structural and functional divergence of cancer hotspot mutations in CREBBP.
Proc.Natl.Acad.Sci.USA, 123:e2605702123-e2605702123, 2026

PubMed Abstract: is among the most frequently mutated genes in human cancer and encodes a lysine acetyltransferase (KAT) protein that acetylates histones and nonhistone proteins to drive transcriptional activation. Mutations of most frequently result in missense changes affecting the active site within the KAT domain. However, there has not yet been comprehensive biochemical, structural, and functional studies to determine the impact of recurrent KAT-domain variants. Here we show that the most frequently mutated residue of , arginine 1446, alters the stability of acetyl-CoA binding within the cofactor-binding pocket but retains detectable acetyltransferase activity for a variety of substrates including histones. In contrast, other recurrently mutated residues affect the catalytic center within the KAT domain and result in a catalytically dead protein with a profound loss of histone acetylation and enhancer activity. These results highlight functionally divergent classes of mutations depending on the position of the mutated residue within KAT domain.

PubMed: 42771512
DOI: 10.1073/pnas.2605702123

Experimental method

X-RAY DIFFRACTION (2.545 Å)