title: Molecular dynamics simulations of the coenzyme induced conformational changes of Mycobacterium tuberculosis L-alanine dehydrogenase.
abstract: 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.
authors.affiliation: School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, China.
authors.forename: Baoping
authors.initials: B
authors.lastname: Ling
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.forename: Siwei
authors.initials: S
authors.lastname: Bi
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Jing
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D050788:Alanine Dehydrogenase / Q000737:chemistry*; D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D004795:Enzyme Stability; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009243:NAD / Q000737:chemistry*; D025341:Principal Component Analysis; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D014867:Water; D009243:NAD; D050788:Alanine Dehydrogenase