TY - JOUR T1 - <em>N</em>-Acetyl Transferase 2 Polymorphisms Associated with Isoniazid Pharmacodynamics: Molecular Features for Ligand Interaction JF - Anticancer Research JO - Anticancer Res SP - 3177 LP - 3180 VL - 30 IS - 8 AU - KAZUTO OHKURA AU - KATSUMI FUKINO AU - YASUO SHINOHARA AU - HITOSHI HORI Y1 - 2010/08/01 UR - http://ar.iiarjournals.org/content/30/8/3177.abstract N2 - 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. ER -