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The Role of the Ω-Loop in Regulation of the Catalytic Activity of TEM-Type β-Lactamases

1
Department Chemistry, M.V. Lomonosov Moscow State University, 3, 1, Leninskie gori, Moscow 119991, Russia
2
Institute of Biomedical Chemistry, ul. Pogodinskaya 10, Moscow 119121, Russia
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 854; https://doi.org/10.3390/biom9120854
Received: 22 October 2019 / Revised: 5 December 2019 / Accepted: 9 December 2019 / Published: 11 December 2019
(This article belongs to the Special Issue Beta-Lactamases: Sequence, Structure, Function, and Inhibition)
Bacterial resistance to β-lactams, the most commonly used class of antibiotics, poses a global challenge. This resistance is caused by the production of bacterial enzymes that are termed β-lactamases (βLs). The evolution of serine-class A β-lactamases from penicillin-binding proteins (PBPs) is related to the formation of the Ω-loop at the entrance to the enzyme’s active site. In this loop, the Glu166 residue plays a key role in the two-step catalytic cycle of hydrolysis. This residue in TEM–type β-lactamases, together with Asn170, is involved in the formation of a hydrogen bonding network with a water molecule, leading to the deacylation of the acyl–enzyme complex and the hydrolysis of the β-lactam ring of the antibiotic. The activity exhibited by the Ω-loop is attributed to the positioning of its N-terminal residues near the catalytically important residues of the active site. The structure of the Ω-loop of TEM-type β-lactamases is characterized by low mutability, a stable topology, and structural flexibility. All of the revealed features of the Ω-loop, as well as the mechanisms related to its involvement in catalysis, make it a potential target for novel allosteric inhibitors of β-lactamases. View Full-Text
Keywords: antibiotic resistance; TEM-type β-lactamases; β-lactam antibiotics; Ω-loop; inhibitor antibiotic resistance; TEM-type β-lactamases; β-lactam antibiotics; Ω-loop; inhibitor
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MDPI and ACS Style

Egorov, A.; Rubtsova, M.; Grigorenko, V.; Uporov, I.; Veselovsky, A. The Role of the Ω-Loop in Regulation of the Catalytic Activity of TEM-Type β-Lactamases. Biomolecules 2019, 9, 854.

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