Document Detail

Crystal structure of arylamine N-acetyltransferases: insights into the mechanisms of action and substrate selectivity.
MedLine Citation:
PMID:  23289949     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Arylamine N-acetyltransferases (NATs) are polymorphic xenobiotic metabolizing enzymes catalyzing the acetylation of aromatic amine chemicals of pharmacological/toxicological relevance (drugs, carcinogens). NATs are primordial determinants of the detoxification and/or bioactivation of these compounds. These enzymes are found in prokaryotes and eukaryotes. Several NAT isoenzymes may be present in one organism, and their substrate specificity profile and pattern of tissue expression suggest distinct functional roles.
AREAS COVERED: Many advances in NAT mechanism, substrate specificity, and functional impact of polymorphism have come from crystallographic and NMR studies. To date, the crystal structures of 10 different NAT homologues have been solved, including two human isoforms and several bacterial NATs. The authors present the most recent snapshot in NAT structure differences and similarities. The authors also depict the structural bases of substrate/inhibitor recognition and specificity, cofactor binding, catalytic mechanism, genetic regulation (polymorphism), and enzyme inhibition.
EXPERT OPINION: The determination of other NATs structures will help to develop specific inhibitors of NAT enzymes with potential clinical relevance. In addition, it will contribute to the identification of endogenous substrates and novel functions associated to this family of enzymes.
Xavier Kubiak; Julien Dairou; Jean-Marie Dupret; Fernando Rodrigues-Lima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2013-01-07
Journal Detail:
Title:  Expert opinion on drug metabolism & toxicology     Volume:  9     ISSN:  1744-7607     ISO Abbreviation:  Expert Opin Drug Metab Toxicol     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-19     Completed Date:  2013-08-15     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101228422     Medline TA:  Expert Opin Drug Metab Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  349-62     Citation Subset:  IM    
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC4413, 75013, Paris, France.
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MeSH Terms
Arylamine N-Acetyltransferase / adverse effects,  chemistry*,  pharmacokinetics*
Bacteria / enzymology
Models, Molecular
Polymorphism, Genetic
Substrate Specificity
Xenobiotics / metabolism
Reg. No./Substance:
0/Xenobiotics; EC N-Acetyltransferase

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