title: An old HAT in human p300/CBP and yeast Rtt109.
abstract: The crystal structure of the human p300 histone acetyltransferase (HAT) domain reveals a familiar alpha + beta fold with unique structural elaborations that merit its classification as a third divergent HAT branch alongside the GCN5-related N-acetyltransferase (GNAT) and MYST (MOZ, Ybf2/Sas3, Sas2, Tip60) families. Two key departures from the core GNAT/MYST HAT fold--a long unstructured chain (or "flap") overlaying the acetyl-CoA (AcCoA) binding groove, and a four-alpha-helix "tower" excursion from the main beta-sheet--critically contribute to the recognition and presumptive catalytic machinery of p300/CBP HAT enzymes. Kinetic and mutant analysis of this enlarged residue constellation in p300 (which is distinct from functional fingerprints drawn from GNAT or MYST complexes) led Liu et al., to suggest that p300/CBP works with an unorthodox "hit and run" mechanism that enlists Tyr1467 as the critical catalytic residue. In order to extend the evolutionary testbed for this variant HAT mechanism beyond the thin roll of p300/CBP orthologs, I propose that Rtt109, a novel yeast HAT that has so far eluded classification, is the prototype of a fungal clan of p300-related enzymes that preserve the embellished HAT fold, but further diversify its catalytic options.
authors.forename: J Fernando
authors.initials: JF
authors.lastname: Bazan
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D050881:E1A-Associated p300 Protein / Q000737:chemistry*; D051548:Histone Acetyltransferases / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae; C524041:Rtt109 protein, S pombe