Domain Motions and Functionally-Key Residues of l-Alanine Dehydrogenase Revealed by an Elastic Network Model

International Journal of Molecular Sciences

Xing-Yuan Li²  Jing-Chao Zhang¹  Yan-Ying Zhu²  Ji-Guo Su¹ 

[1] College of Science, Yanshan University, Qinhuangdao 066004, China

关键词: Mycobacterium tuberculosis l-alanine dehydrogenase;    domain motions;    functionally-key residues;    Gaussian network model;    anisotropy network model;    thermodynamic cycle method;   

DOI  :  10.3390/ijms161226170

来源: mdpi

【 摘 要 】

Mycobacterium tuberculosis l-alanine dehydrogenase (l-MtAlaDH) plays an important role in catalyzing l-alanine to ammonia and pyruvate, which has been considered to be a potential target for tuberculosis treatment. In the present work, the functional domain motions encoded in the structure of l-MtAlaDH were investigated by using the Gaussian network model (GNM) and the anisotropy network model (ANM). The slowest modes for the open-apo and closed-holo structures of the enzyme show that the domain motions have a common hinge axis centered in residues Met133 and Met301. Accompanying the conformational transition, both the 1,4-dihydronicotinamide adenine dinucleotide (NAD)-binding domain (NBD) and the substrate-binding domain (SBD) move in a highly coupled way. The first three slowest modes of ANM exhibit the open-closed, rotation and twist motions of l-MtAlaDH, respectively. The calculation of the fast modes reveals the residues responsible for the stability of the protein, and some of them are involved in the interaction with the ligand. Then, the functionally-important residues relevant to the binding of the ligand were identified by using a thermodynamic method. Our computational results are consistent with the experimental data, which will help us to understand the physical mechanism for the function of l-MtAlaDH.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.