Structure-function analyses of single nucleotide polymorphisms in human N-acetyltransferase 1

被引：10

作者：

Walraven, Jason M. ^{[1
,2
]}

Trent, John O. ^{[1
,2
]}

Hein, David W. ^{[1
,2
]}

机构：

[1] Univ Louisville, Sch Med, Dept Pharmacol, James Graham Brown Canc Ctr, Louisville, KY 40292 USA

[2] Univ Louisville, Sch Med, Dept Toxicol & Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA

来源：

DRUG METABOLISM REVIEWS | 2008年 / 40卷 / 01期

关键词：

NAT1; N-acetyltransferase; 1; single nucleotide polymorphisms (SNPs); structure-function relationships; cancer susceptibility; birth defects;

D O I：

10.1080/03602530701852917

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：169 / 184

页数：16

共 55 条

[1]

Adam PJ, 2003, MOL CANCER RES, V1, P826

[2] Hair dye use, meat intake, and tobacco exposure and presence of carcinogen-DNA adducts in exfoliated breast ductal epithelial cells [J].

Ambrosone, Christine B. ;

Abrams, Sara M. ;

Gorlewska-Roberts, Katarzyna ;

Kadlubar, Fred F. .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2007, 464 (02) :169-175

[3]

BELL DA, 1995, CANCER RES, V55, P3537

[4] Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma [J].

Bièche, I ;

Girault, I ;

Urbain, E ;

Tozlu, S ;

Lidereau, R .

BREAST CANCER RESEARCH, 2004, 6 (03) :R252-R263

[5] Arylamine N-acetyltransferases:: What we learn from genes and genomes [J].

Boukouvala, S ;

Fakis, G .

DRUG METABOLISM REVIEWS, 2005, 37 (03) :511-564

[6] Correlation between genotype and phenotype of the human arylamine N-acetyltransferase type 1 (NAT1) [J].

Bruhn, C ;

Brockmöller, J ;

Cascorbi, I ;

Roots, I ;

Borchert, HH .

BIOCHEMICAL PHARMACOLOGY, 1999, 58 (11) :1759-1764

[7] Proteasomal degradation of N-acetyltransferase 1 is prevented by acetylation of the active site cysteine -: A mechanism for the slow acetylator phenotype and substrate-dependent down-regulation [J].

Butcher, NJ ;

Arulpragasam, A ;

Minchin, RF .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (21) :22131-22137

[8] Risk of limb deficiency defects associated with NAT1, NAT2, GSTT1, GSTM1, and NOS3 genetic variants, maternal smoking, and vitamin supplement intake [J].

Carmichael, Suzan L. ;

Shaw, Gary M. ;

Yang, Wei ;

Iovannisci, David M. ;

Lammer, Edward .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2006, 140A (18) :1915-1922

[9]

Chen J, 1998, CANCER RES, V58, P3307

[10] Characterization of naturally occurring and recombinant human N-acetyltransferase variants encoded by NAT1 [J].

de León, JH ;

Vatsis, KP ;

Weber, WW .

MOLECULAR PHARMACOLOGY, 2000, 58 (02) :288-299

← 1 2 3 4 5 6 →