The pharmacogenetics of NAT: structural aspects.

Abstract:

:Arylamine N-acetyltransferases (NATs) catalyze the transfer of an acetyl group from acetyl-CoA to arylhydrazines and to arylamine drugs and carcinogens or to their N-hydroxylated metabolites. NAT plays an important role in detoxification and metabolic activation of xenobiotics and was first identified as the enzyme responsible for inactivation of the antitubercular drug isoniazid, an arylhydrazine. The rate of inactivation was polymorphically distributed in the population: the first example of interindividual pharmacogenetic variation. Polymorphism in NAT activity is primarily due to single nucleotide polymorphisms (SNPs) in the coding region of NAT genes. NAT enzymes are widely distributed in eukaryotes and genome sequences have revealed many homologous members of this enzyme family in prokaryotes. The structures of S almonella typhimurium and Mycobacterium smegmatis NATs have been determined, revealing a unique fold in which a catalytic triad (Cys-His-Asp) forms the active site. Determination of prokaryotic and eukaryotic NAT structures could lead to a better understanding of their role in xenobiotics and endogenous metabolism.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Pompeo F,Brooke E,Kawamura A,Mushtaq A,Sim E

doi

10.1517/14622416.3.1.19

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

19-30

issue

1

eissn

1462-2416

issn

1744-8042

pii

PGS030108

journal_volume

3

pub_type

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