Molecular dynamics simulations of the coenzyme induced conformational changes of Mycobacterium tuberculosisl-alanine dehydrogenase

Mycobacterium tuberculosisl-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.

Based on the crystal structures, molecular dynamics simulations were performed to investigate the conformational changes of l-MtAlaDH induced by coenzyme NADH. The results show that the presence of coenzyme NADH in NAD-binding domain restricts the motions and conformational distributions of l-MtAlaDH. Two loops (residues 94–99 and 238–251) play important roles in the binding of NADH, while the other loop (residues 267–293) is responsible for the binding of the substrate; the opening/closing and twisting motions are directly related to conformational changes of l-MtAlaDH induced by NADH.Figure optionsDownload high-quality image (222 K)Download as PowerPoint slideHighlights
► The conformational changes of l-MtAlaDH induced by coenzyme NADH were studied.
► The presence of NDAH restricts the motions and conformational changes of protein.
► The loops and α-helixes participate in the binding/releasing of the substrate/product.
► The opening/closing and twisting motions of interdomains of protein were directly related to the conformational changes of l-MtAlaDH.