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

J Mol Graph Model. 2012 May:35:1-10. doi: 10.1016/j.jmgm.2012.01.005. Epub 2012 Feb 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Dehydrogenase / chemistry*
  • Algorithms
  • Bacterial Proteins / chemistry*
  • Binding Sites
  • Enzyme Stability
  • Hydrogen Bonding
  • Molecular Dynamics Simulation*
  • Mycobacterium tuberculosis / enzymology*
  • NAD / chemistry*
  • Principal Component Analysis
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thermodynamics
  • Water / chemistry

Substances

  • Bacterial Proteins
  • Water
  • NAD
  • Alanine Dehydrogenase