文章基本信息

标题：Computational Study of the Three-Dimensional Structure of N-Acetyltransferase 2–Acetyl Coenzyme A Complex
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作者：Akifumi Oda ; Kana Kobayashi ; Ohgi Takahashi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：10
页码：1639-1643
DOI：10.1248/bpb.33.1639
出版社：The Pharmaceutical Society of Japan
摘要：N -Acetyltransferase 2 (NAT2) is one of the most important polymorphic drug-metabolizing enzymes and plays a significant role in individual differences of drug efficacies and/or side effects. Coenzyme A (CoA) is a cofactor in the experimentally determined crystal structure of NAT2, although the acetyl source of acetylation reactions catalyzed by NAT is not CoA, but rather acetyl CoA. In this study, the three-dimensional structure of NAT2, including acetyl CoA, was calculated using molecular dynamics simulation. By substituting acetyl CoA for CoA the amino acid residue Gly286, which is known to transform into a glutamate residue by NAT2*7A and NAT2*7B , comes close to the cofactor binding site. In addition, the binding pocket around the sulfur atom of acetyl CoA expanded in the NAT2–acetyl CoA complex.
关键词：N-acetyltransferase;genetic polymorphism;acetyl CoA;molecular dynamics simulation