Structure-function analyses of single nucleotide polymorphisms in human N-acetyltransferase 1.
Human N-acetyltransferase 1 (NAT1) alleles are characterized by one or more single nucleotide polymorphisms (SNPs) associated with rapid and slow acetylation phenotypes. NAT1 both activates and deactivates arylamine drugs and carcinogens, and NAT1 polymorphisms are associated with increased frequencies of many cancers and birth defects. The recently resolved human NAT1 crystal structure was used to evaluate SNPs resulting in the protein substitutions R64W, V149I, R187Q, M205V, S214A, D251V, E261K, and I263V. The analysis enhances knowledge of NAT1 structure-function relationships, important for understanding associations of NAT1 SNPs with genetic predisposition to cancer, birth defects, and other diseases.
Walraven
Jason M
JM
Department of Pharmacology & Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
Trent
John O
JO
Hein
David W
DW
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000737:chemistry / Q000235:genetics; D000013:Congenital Abnormalities / Q000201:enzymology / Q000235:genetics; D018360:Crystallography, X-Ray; D020022:Genetic Predisposition to Disease; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation
D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1