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    
Abstract/OtherAbstract:
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.
Authors:
Xavier Kubiak; Julien Dairou; Jean-Marie Dupret; Fernando Rodrigues-Lima
Related Documents :
21325689 - Glycolytic enzyme activity is essential for domestic cat (felis catus) and cheetah (aci...
23272109 - Suites of terpene synthases explain differential terpenoid production in ginger and tur...
1733969 - Purification of the secretor-type beta-galactoside alpha 1----2-fucosyltransferase from...
640589 - Differences in intracellular corrective activity in cultured mannosidosis cells of acid...
7369919 - Effect of fluoride on alpha-chymotrypsin.
6279579 - Purification and properties of alpha-galactosidase from immature stalks of saccharum of...
1276179 - The effects of proteolytic enzymes on the mechanical properties of adult human articula...
3494449 - Inhibition of mitochondrial alpha-ketoglutarate dehydrogenase by 1-methyl-4-phenylpyrid...
2939589 - The initiation of fibrinolysis in alpha 2-plasmin inhibitor deficient plasma. role of f...
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    
Affiliation:
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC4413, 75013, Paris, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetylation
Arylamine N-Acetyltransferase / adverse effects,  chemistry*,  pharmacokinetics*
Bacteria / enzymology
Biotransformation
Humans
Models, Molecular
Polymorphism, Genetic
Substrate Specificity
Xenobiotics / metabolism
Chemical
Reg. No./Substance:
0/Xenobiotics; EC 2.3.1.5/Arylamine N-Acetyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Structural and functional characteristics of cGMP-dependent methionine oxidation in Arabidopsis thal...
Next Document:  Comparison of percent density from raw and processed full field digital mammography data.