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

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• 作者：Baoping Ling^a ; Min Sun^a ; Siwei Bi^a ; Zhihong Jing^a ; Yongjun Liu^b ; ^c ; ^{yongjunliu_1@sdu.edu.cn}
• 关键词：l-Alanine dehydrogenase ; Mycobacterium tuberculosis ; Principle component analysis ; Free energy landscape ; Molecular dynamics simulations
• 刊名：Journal of Molecular Graphics and Modelling
• 出版年：2012
• 期刊代码：77_10933263
• 类别：cp
• 出版时间：May, 2012
• 卷：35
• 期：Complete
• 页码：1-10
• 文件大小：3507 K

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.