title: Identification of a novel allele at the human NAT1 acetyltransferase locus.
abstract: Humans possess two N-acetyltransferase isozymes (NAT1 and NAT2). We cloned and sequenced a novel NAT1 allele (Genbank HSU 80835) that contained nucleotide substitutions at -344 (C-->T), -40 (A-->T), 445 [G-->A(Val-->Ile)], 459 [G-->A(silent)], 640 [T-->G(Ser-->Ala)], a 9 base pair deletion between nucleotides 1065 and 1090, and 1095 (C-->A). The novel NAT1 allele which we have designated NAT1*17 is similar to NAT1*11 except for a G445A substitution (Val149-->Ile) in the NAT1 coding region. The G445A (Val149-->Ile) substitution yielded no significant changes in levels of immunoreactivity, as detected by Western blot, nor in intrinsic stability of the recombinant N-acetyltransferase protein. However, the G445A (Val149-->Ile) substitution yielded expression of recombinant NAT1 protein that catalyzed the N-acetylation of aromatic amines and the O- and N,O-acetylation of their N-hydroxylated metabolites at rates up to 2-fold higher than wild-type recombinant human NAT1.
authors.affiliation: Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202-9037, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Doll
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.forename: A C
authors.initials: AC
authors.lastname: Deitz
authors.forename: T D
authors.initials: TD
authors.lastname: Rustan
authors.forename: D W
authors.initials: DW
authors.lastname: Hein
mesh_terms: D000107:Acetylation; D000483:Alleles; D000595:Amino Acid Sequence; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002678:Chimera / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004795:Enzyme Stability; D005818:Genetic Engineering; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D011994:Recombinant Proteins; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1