Bacterial class A serine β-lactamase enzyme (Class A β-lactamase)

Class A serine β-lactamases are bacterial enzymes responsible for mediating resistance to β-lactam antibiotics through hydrolysis of their characteristic β-lactam ring, rendering the drugs ineffective[1][2][3]. These enzymes are widely distributed among both Gram-negative and Gram-positive bacteria and have given rise to major resistance variants such as TEM, SHV, CTX-M, and KPC[3][5][9]. Catalysis occurs via a conserved active-site serine, forming a covalent acyl-enzyme intermediate, which is subsequently hydrolyzed with the help of an activated water molecule coordinated by critical active-site residues[3][5][7][9]. This enzymatic activity poses a significant challenge to infection management, as it can lead to therapeutic failures. Class A serine β-lactamases are the molecular targets for drug development, including β-lactamase inhibitors, but their evolutionary flexibility and tendency for mutations have complicated treatment efforts[2][3][5][9].

Other names

Serine β-lactamaseClass A β-lactamaseTEM, SHV, CTX-M, KPC (common subfamilies or enzyme types within class A)

Drug hydrolysis: The enzyme uses an active-site serine to covalently bind and hydrolyze the β-lactam ring, completely inactivating the antibiotic; Antagonism: Certain drugs (β-lactamase inhibitors) can bind the enzyme and reduce its activity, restoring antibiotic efficacy in some cases