1QSR

CRYSTAL STRUCTURE OF TETRAHYMENA GCN5 WITH BOUND ACETYL-COENZYME A

Summary for 1QSR

• Entry DOI: 10.2210/pdb1qsr/pdb
• Descriptor: TGCN5 HISTONE ACETYL TRANSFERASE, ACETYL COENZYME *A (3 entities in total)
• Functional Keywords: histone acetyltransferase, gcn5-related n-acetyltransferase, coa-binding protein, transferase
• Biological source: Tetrahymena thermophila
• Total number of polymer chains: 1
• Total formula weight: 20154.07

Authors

Rojas, J.R.,Trievel, R.C.,Zhou, J.,Mo, Y.,Li, X.,Berger, S.L.,David Allis, C.,Marmorstein, R. (deposition date: 1999-06-23, release date: 1999-09-08, Last modification date: 2024-02-14)

Primary citation

Rojas, J.R.,Trievel, R.C.,Zhou, J.,Mo, Y.,Li, X.,Berger, S.L.,Allis, C.D.,Marmorstein, R.
Structure of Tetrahymena GCN5 bound to coenzyme A and a histone H3 peptide.
Nature, 401:93-98, 1999

PubMed Abstract: Gene activation is a highly regulated process that requires the coordinated action of proteins to relieve chromatin repression and to promote transcriptional activation. Nuclear histone acetyltransferase (HAT) enzymes provide a mechanistic link between chromatin destabilization and gene activation by acetylating the epsilon-amino group of specific lysine residues within the aminoterminal tails of core histones to facilitate access to DNA by transcriptional activators. Here we report the high-resolution crystal structure of the HAT domain of Tetrahymena GCN5 (tGCN5) bound with both its physiologically relevant ligands, coenzyme A (CoA) and a histone H3 peptide, and the structures of nascent tGCN5 and a tGCN5/acetyl-CoA complex. Our structural data reveal histone-binding specificity for a random-coil structure containing a G-K-X-P recognition sequence, and show that CoA is essential for reorienting the enzyme for histone binding. Catalysis appears to involve water-mediated proton extraction from the substrate lysine by a glutamic acid general base and a backbone amide that stabilizes the transition-state reaction intermediate. Comparison with related N-acetyltransferases indicates a conserved structural framework for CoA binding and catalysis, and structural variability in regions associated with substrate-specific binding.

PubMed: 10485713
DOI: 10.1038/43487

Experimental method

X-RAY DIFFRACTION (2 Å)