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

Department Chemistry, M.V. Lomonosov Moscow State University, 3, 1, Leninskie gori, Moscow 119991, Russia
Institute of Biomedical Chemistry, ul. Pogodinskaya 10, Moscow 119121, Russia
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 854;
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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