Structure-Function Analyses of Single Nucleotide Polymorphisms in Human N-Acetyltransferase 1

Abstract

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.

Key Words :

• NAT1
• N-acetyltransferase 1
• Single nucleotide polymorphisms (SNPs)
• Structure-function relationships
• Cancer susceptibility
• Birth defects.

Acknowledgments

The studies were partially supported by National Institutes of Health grants R01-CA034627 (DWH) and T32-ES011564 (DWH to support JMW). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.