Detailed investigation of catalytically important residues of class A β-lactamase.

An increasing global health challenge is antimicrobial resistance. Bacterial infections are often treated by using β-lactam antibiotics. But several resistance mechanisms have evolved in clinically mutated bacteria, which results in resistance against such antibiotics. Among which production of novel β-lactamase is the major one. This results in bacterial resistance against penicillin, cephalosporin, and carbapenems, which are considered to be the last resort of antibacterial treatment. Hence, β-lactamase enzymes produced by such bacteria are called extended-spectrum β-lactamase and carbapenemase enzymes. Further, these bacteria have developed resistance against many β-lactamase inhibitors as well. So, investigation of important residues that play an important role in altering and expanding the spectrum activity of these β-lactamase enzymes becomes necessary. This review aims to gather knowledge about the role of residues and their mutations in class A β-lactamase, which could be responsible for β-lactamase mediated resistance. Class A β-lactamase enzymes contain most of the clinically significant and expanded spectrum of β-lactamase enzymes. Ser70, Lys73, Ser130, Glu166, and Asn170 residues are mostly conserved and have a role in the enzyme's catalytic activity. In-depth investigation of 69, 130, 131, 132, 164, 165, 166, 170, 171, 173, 176, 178, 179, 182, 237, 244, 275 and 276 residues were done along with its kinetic analysis for knowing its significance. Further, detailed information from many previous studies was gathered to know the effect of mutations on the kinetic activity of class A β-lactamase enzymes with β-lactam antibiotics.Communicated by Ramaswamy H. Sarma.