摘要
Mycobacterium tuberculosis l-alanine dehydrogenase (l-MtAlaDH) catalyzes the NADH-dependent reversible oxidative deamination of l-alanine to pyruvate and ammonia. l-MtAlaDH has been proposed to be a potential target in the treatment of tuberculosis. Based on the crystal structures of this enzyme, molecular dynamics simulations were performed to investigate the conformational changes of l-MtAlaDH induced by coenzyme NADH. The results show that the presence of NADH in the binding domain restricts the motions and conformational distributions of l-MtAlaDH. There are two loops (residues 94-99 and 238-251) playing important roles for the binding of NADH, while another loop (residues 267-293) is responsible for the binding of substrate. The opening/closing and twisting motions of two domains are closely related to the conformational changes of l-MtAlaDH induced by NADH.