Investigation the role of mutations M182T and Q39K in structure of beta-lactamase TEM-72 by molecular dynamics method

   
Shcherbinin D.S.1, Rubtsova M.Yu.2, Grigorenko V.G.2, Uporov I.V.2, Veselovsky A.V.1 , Egorov A.M.2

1. Institute of Biomedical Chemistry, Moscow, Russia
2. Lomonosov Moscow State University, Chemical Department, Moscow, Russia
Section: Bioinformatics/Proteomics
DOI: 10.18097/PBMC20166205527      PubMed Id: 27797327
Year: 2016  Volume: 62  Issue: 5  Pages: 527-534
Synthesis of b-lactamases is one of the common mechanisms of bacterial resistance to b-lactam antibiotics including penicillins and cephalosporins. The widespread use of antibiotics results in appearance of numerous extended-spectrum b-lactamase variants or resistance to inhibitors. Mutations of 92 residues of TEM type were found. Several mutations are the key mutations that determine the extension of spectrum of substrates. However, roles of the most associated mutations, located far from active site, remain unknown. We have investigated the role of associated mutations in structure of b-lactamase TEM-72, which contain two key mutation (G238S, E240K) and two associated mutations (Q39K, M182T) by means of simulation of molecular dynamics. The key mutation lead to destabilization of the protein globule, characterized by increased mobility of amino acid residues at high temperature of modelling. Mutation M182T lead to stabilization protein, whereas mutation Q39K is destabilizing mutation. It seems that the last mutation serves for optimization of conformational mobility of b-lactamase and may influence on enzyme activity.
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Keywords: beta-lactamase, TEM-1, TEM-72, mutations, thermoresistance, molecular dynamics
Citation:

Shcherbinin, D. S., Rubtsova, M. Yu., Grigorenko, V. G., Uporov, I. V., Veselovsky, A. V., Egorov, A. M. (2016). Investigation the role of mutations M182T and Q39K in structure of beta-lactamase TEM-72 by molecular dynamics method. Biomeditsinskaya khimiya, 62(5), 527-534.
This paper is also available as the English translation: 10.1134/S1990750817020056
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