RT Journal Article SR Electronic T1 N-Acetyl Transferase 2 Polymorphisms Associated with Isoniazid Pharmacodynamics: Molecular Features for Ligand Interaction JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3177 OP 3180 VO 30 IS 8 A1 OHKURA, KAZUTO A1 FUKINO, KATSUMI A1 SHINOHARA, YASUO A1 HORI, HITOSHI YR 2010 UL http://ar.iiarjournals.org/content/30/8/3177.abstract AB Background: Isoniazid is mainly metabolized by arylamine N-acetyltransferase 2 (NAT2). Rapid acetylator types have NAT2*4/*4 alleles. Intermediate acetylator types have any of the following alleles: NAT2*4/*5, *4/*6, or *4/*7. Slow acetylator types do not have the NAT2*4 allele. We examined molecular features of these NAT2 molecules. Materials and Methods: Structures of NAT2*5, *6, and *7 were constructed based on X-ray data of human NAT2*4 using a molecular modeling technique. Results: The NAT2*4 molecule mostly occupied a positive electrostatic potential field. Ile114 and Arg197, which are mutation sites of NAT2*4 to NAT2*5 and NAT2*6, were located in the peripheral part of the positive field. Gly286, the mutation site from NAT2*4 to NAT2*7, was located near coenzyme A (CoA) in the boundary of the positive and negative fields. Conclusion: Nonbinding energies between NAT2s and isoniazid were larger than those of CoA. Molecular polymorphism appears to influence the reactivity between NAT2 and the external ligand.