Identification of a novel allele at the human NAT1 acetyltransferase locus.

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. -->
Grant Information: CA-34627 United States CA NCI NIH HHS
Molecular Sequence: GENBANK U80835
Substance Nomenclature: 0 (DNA Primers)
0 (Isoenzymes)
0 (Recombinant Proteins)
EC 2.3.1.5 (Arylamine N-Acetyltransferase)
EC 2.3.1.5 (N-acetyltransferase 1)
Entry Date(s): Date Created: 19970428 Date Completed: 19970630 Latest Revision: 20071114
Update Code: 20231215
DOI: 10.1006/bbrc.1997.6501
PMID: 9168895
Autor: Doll MA; Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202-9037, USA., Jiang W, Deitz AC, Rustan TD, Hein DW
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1997 Apr 28; Vol. 233 (3), pp. 584-91.
DOI: 10.1006/bbrc.1997.6501
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: