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Updated: Jun 8, 2026

Collecting Variable-concentration Isothermal Titration Calorimetry Datasets in Order to Determine Binding Mechanisms
Published on: April 7, 2011
N-acetyl transferase 2 polymorphisms associated with isoniazid pharmacodynamics: molecular features for ligand
Kazuto Ohkura1, Katsumi Fukino, Yasuo Shinohara
1Faculty of Pharmacy, Chiba Institute of Science, 3 Shiomi-cho, Choshi, Chiba 288-0025, Japan. kohkura@sag.bekkoame.ne.jp
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. Ile(114) and Arg(197), which are mutation sites of NAT2*4 to NAT2*5 and NAT2*6, were located in the peripheral part of the positive field. Gly(286), 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.
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