title: The histone acetyltransferase NCOAT contains a zinc finger-like motif involved in substrate recognition.
abstract: Nuclear cytoplasmic O-GlcNAcase and acetyltransferase (NCOAT) is a bifunctional enzyme with both glycoside hydrolase and alkyltransferase activity. Its O-GlcNAcase active site lies in the N terminus of the enzyme and its histone acetyltransferase (HAT) domain lies in the C terminus. Whereas the HAT domain of the enzyme is catalytically and structurally similar to other acetyltransferases across subfamilies, NCOAT has a motif resembling a zinc finger-like domain unique to the MYST family of HATs. Among the MYST family, this zinc finger, or zinc finger-like domain, is responsible for making contacts with the histone tails within nucleosomes for the HAT to catalyze its respective reaction. Here, we show that NCOAT has the ability to directly associate with both an acetylated and unacetylated histone H4 tail in vitro, and a potential zinc finger-like motif found in NCOAT is implicated in this nucleosomal contact, and is necessary for fully efficient enzymatic activity. Subsequent to the catalysis of acetyltransfer to lysine 8 of histone H4 for the enzyme, however, the substrate is released and NCOAT can no longer bind H4 in our assays. Furthermore, this finger domain by itself is sufficient to bind histone H4.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama, Birmingham, 35294-0012, USA.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Toleman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Paterson
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Kudlow
mesh_terms: D000118:Acetylglucosaminidase / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D004229:Dithiothreitol / Q000494:pharmacology; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers; D001619:beta-N-Acetylhexosaminidases
chemical_list: D006657:Histones; D009097:Multienzyme Complexes; D051548:Histone Acetyltransferases; C110628:hexosaminidase C; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases; D004229:Dithiothreitol