1YGH

HAT DOMAIN OF GCN5 FROM SACCHAROMYCES CEREVISIAE

Summary for 1YGH

• Entry DOI: 10.2210/pdb1ygh/pdb
• Descriptor: PROTEIN (TRANSCRIPTIONAL ACTIVATOR GCN5), GLYCEROL (3 entities in total)
• Functional Keywords: transcriptional regulation, histone acetylation, n-acetyltransferase, gcn5 related n-acetyltransferase family, gene regulation
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Total number of polymer chains: 2
• Total formula weight: 38681.10

Authors

Trievel, R.C.,Rojas, J.R.,Sterner, D.E.,Venkataramani, R.,Wang, L.,Zhou, J.,Allis, C.D.,Berger, S.L.,Marmorstein, R. (deposition date: 1999-05-27, release date: 1999-08-02, Last modification date: 2024-04-03)

Primary citation

Trievel, R.C.,Rojas, J.R.,Sterner, D.E.,Venkataramani, R.N.,Wang, L.,Zhou, J.,Allis, C.D.,Berger, S.L.,Marmorstein, R.
Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator.
Proc.Natl.Acad.Sci.USA, 96:8931-8936, 1999

PubMed Abstract: The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Here, we present the high resolution crystal structure of the HAT domain of yGCN5 and probe the functional importance of a conserved glutamate residue. The structure reveals a central protein core associated with AcCoA binding that appears to be structurally conserved among a superfamily of N-acetyltransferases, including yeast histone acetyltransferase 1 and Serratia marcescens aminoglycoside 3-N-acetyltransferase. A pronounced cleft lying above this core, and flanked by N- and C-terminal regions that show no sequence conservation within N-acetyltransferase enzymes, is implicated by cross-species conservation and mutagenesis studies to be a site for histone substrate binding and catalysis. Located at the bottom of this cleft is a conserved glutamate residue (E173) that is in position to play an important catalytic role in histone acetylation. Functional analysis of an E173Q mutant yGCN5 protein implicates glutamate 173 to function as a general base for catalysis. Together, a correlation of the yGCN5 structure with functionally debilitating yGCN5 mutations provides a paradigm for understanding the structure/function relationships of the growing number of transcriptional regulators that function as histone acetyltransferase enzymes.

PubMed: 10430873
DOI: 10.1073/pnas.96.16.8931

Experimental method

X-RAY DIFFRACTION (1.9 Å)