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Bacterial TEM-Type Serine Beta-Lactamases: Structure and Analysis of Mutations

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Abstract

Beta-lactamases (EC 3.5.2.6) represent a superfamily containing more than 2000 members: it includes genetically and functionally different bacterial enzymes capable to degrade the beta-lactam antibiotics. Beta-lactamases of molecular class A with serine residue in the active center are the most common ones. In the context of studies of the mechanisms underlying of evolution of the resistance, TEM type beta-lactamases are of particular interest due to their broad polymorphism. To date, more than 200 sequences of TEM type beta-lactamases have been described and more than 60 structures of different mutant forms of these enzymes have been presented in the Protein Data Bank. We have considered here the main structural features of the enzymes of this type with particular attention to the analysis of key mutations determining drug resistance and the secondary mutations, their location relative to the active center and the surface of the protein globule. We have developed a BlaSIDB database (www.blasidb.org) which is an open information resource combining available data on 3D structures, amino acid sequences and nomenclature of the TEM type beta-lactamases.

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Abbreviations

BlaSIDB:

beta-lactamase structure information database

ESBL:

extended spectrum β-lactamases

PDB:

Protein Data Bank

SASA:

solvent accessible surface area

WHO:

World Health Organization

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Correspondence to V. G. Grigorenko.

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Original Russian Text © V.G. Grigorenko, M.Yu. Rubtsova, I.V. Uporov, I.V. Ishtubaev, I.P. Andreeva, D.S. Shcherbinin, A.V. Veselovsky, A.M. Egorov, 2018, published in Biomeditsinskaya Khimiya.

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Grigorenko, V.G., Rubtsova, M.Y., Uporov, I.V. et al. Bacterial TEM-Type Serine Beta-Lactamases: Structure and Analysis of Mutations. Biochem. Moscow Suppl. Ser. B 12, 87–95 (2018). https://doi.org/10.1134/S1990750818020038

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  • DOI: https://doi.org/10.1134/S1990750818020038

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