Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator
10.1073/pnas.96.16.8931
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
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.

Bibliography

Trievel, R. C., Rojas, J. R., Sterner, D. E., Venkataramani, R. N., Wang, L., Zhou, J., Allis, C. D., Berger, S. L., & Marmorstein, R. (1999). Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator. Proceedings of the National Academy of Sciences, 96(16), 8931–8936.

Authors 9 University of Pennsylvania
  1. Raymond C. Trievel (first) University of Pennsylvania
  2. Jeannie R. Rojas (additional) University of Pennsylvania
  3. David E. Sterner (additional) University of Pennsylvania
  4. Ravichandran N. Venkataramani (additional) University of Pennsylvania
  5. Lian Wang (additional) University of Pennsylvania
  6. Jianxin Zhou (additional) University of Pennsylvania
  7. C. David Allis (additional) University of Pennsylvania
  8. Shelley L. Berger (additional) University of Pennsylvania
  9. Ronen Marmorstein (additional) University of Pennsylvania
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Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 10:41 a.m.)
Deposited 3 years, 2 months ago (June 7, 2022, 12:37 a.m.)
Indexed 2 days, 16 hours ago (Aug. 29, 2025, 5:40 a.m.)
Issued 26 years ago (Aug. 3, 1999)
Published 26 years ago (Aug. 3, 1999)
Published Online 26 years ago (Aug. 3, 1999)
Published Print 26 years ago (Aug. 3, 1999)
Funders 0

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@article{Trievel_1999, title={Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.16.8931}, DOI={10.1073/pnas.96.16.8931}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Trievel, Raymond C. and Rojas, Jeannie R. and Sterner, David E. and Venkataramani, Ravichandran N. and Wang, Lian and Zhou, Jianxin and Allis, C. David and Berger, Shelley L. and Marmorstein, Ronen}, year={1999}, month=aug, pages={8931–8936} }