title: Writers and readers of histone acetylation: structure, mechanism, and inhibition.
abstract: Histone acetylation marks are written by histone acetyltransferases (HATs) and read by bromodomains (BrDs), and less commonly by other protein modules. These proteins regulate many transcription-mediated biological processes, and their aberrant activities are correlated with several human diseases. Consequently, small molecule HAT and BrD inhibitors with therapeutic potential have been developed. Structural and biochemical studies of HATs and BrDs have revealed that HATs fall into distinct subfamilies containing a structurally related core for cofactor binding, but divergent flanking regions for substrate-specific binding, catalysis, and autoregulation. BrDs adopt a conserved left-handed four-helix bundle to recognize acetyllysine; divergent loop residues contribute to substrate-specific acetyllysine recognition.
authors.affiliation: Program in Gene Expression and Regulation, Wistar Institute, and Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
authors.forename: Ronen
authors.initials: R
authors.lastname: Marmorstein
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10065.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary
chemical_list: D002843:Chromatin; D004791:Enzyme Inhibitors; D006657:Histones; D051548:Histone Acetyltransferases