title: Structure of histone acetyltransferases.
abstract: Histone acetyltranferase (HAT) enzymes are the catalytic subunits of multisubunit protein complexes that acetylate specific lysine residues on the N-terminal regions of the histone components of chromatin to promote gene activation. These enzymes, which now include more than 20 members, fall into distinct families that generally have high sequence similarity and related substrate specificity within families, but have divergent sequence and substrate specificity between families. Significant insights into the mode of catalysis and histone substrate binding have been provided by the structure determination of the divergent HAT enzymes Hat1, Gcn5/PCAF and Esa1. A comparison of these structures reveals a structurally conserved central core domain that mediates extensive interactions with the acetyl-coenzyme A cofactor, and structurally divergent N and C-terminal domains. A correlation of these structures with other studies reveals that the core domain plays a particularly important role in histone substrate catalysis and that the N and C-terminal domains play important roles in histone substrate binding. These correlations imply a related mode of catalysis and histone substrate binding by a diverse group of HAT enzymes.
authors.affiliation: The Wistar Institute and the Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA. marmor@wistar.upenn.edu
authors.forename: R
authors.initials: R
authors.lastname: Marmorstein
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D051548:Histone Acetyltransferases; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D014158:Transcription, Genetic
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D051548:Histone Acetyltransferases