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Evolutionary insights into the active-site structures of the metallo-β-lactamase superfamily from a classification study with support vector machine

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Abstract

The metallo-β-lactamase (MβL) superfamily, which is intriguing due to its enzyme promiscuity, is a good model enzyme superfamily for studies of catalytic function evolution. Our previous study traced the evolution of the phosphotriesterase activity of the MβL superfamily and found that MβLs go through three typical active-site structures in the development of phosphotriesterase activity. In the present study, taking the three typical active-site structures as class labels, the classification and prediction models, which were established by support vector machine and amino acid composition, classified the MβL members into three classes. The indispensable amino acid compositions showed a surprising performance that was remarkably better than the performance of the dispensable amino acid compositions and even equal to the performance of the 20 native amino acids. We further traced the origin of the classification error and found that there was one subclass adopting a type of active-site structure that was the evolutionary transition between these classes. After that, our classification and prediction models were successfully used to predict several MβL active-site structures that lost the dinuclear structures during crystallization. In summary, our studies established a classification and prediction system for active-site structures that well compensated for experimental methods that recognize protein structure details and suggest that the indispensable amino acids contain much more protein structure information than the dispensable amino acids.

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Data availability

Some or all data and models used during the study are available from the corresponding author by request.

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All the code used during the study is available from the corresponding author by request.

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Acknowledgements

This work was supported by grants from the Natural Science Foundation of China (Grant no. 21203042), the Fundamental Research Funds for the Central Universities of Northwest Minzu University of China (Grant no. 31920200038), the Scientific Research Program of the Higher Education Institutions of Gansu Province (Grant no. 2020A-016), and the Foundation of Northwest Normal University of China (Grant no. NWNU-LKQN2019-18).

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  1. College of Physics and Electronic Engineering, Northwest Normal University, Lanzhou, 730070, People’s Republic of China

    Lili Wang

  2. MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Institute of Theoretical and Simulation Chemistry, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150080, People’s Republic of China

    Ling Yang

  3. Biomedical Research Center, College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, People’s Republic of China

    Yu-lan Feng & Hao Zhang

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  1. Lili Wang
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Wang, L., Yang, L., Feng, Yl. et al. Evolutionary insights into the active-site structures of the metallo-β-lactamase superfamily from a classification study with support vector machine. J Biol Inorg Chem 25, 1023–1034 (2020). https://doi.org/10.1007/s00775-020-01822-y

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