Antibiotic resistance in gram-negative bacteria has emerged as a major health threat that occurs
because these bacteria actively produce β-lactamases responsible for the inactivation of β-lactam
antibiotics. The first β lactamase was reported in E. coli back in 1940, before the release of the first antibiotic
penicillin in clinical settings. Later on, large numbers of β-lactamases have been discovered in
Gram-positive, Gram-negative bacteria as well as mycobacteria. Currently, numerous three-dimensional
structures of serine and metallo-β-lactamases have been solved. The serine β-lactamases essentially consist
of two structural domains (an all α and an α/β domain) and the active site is located at the groove
between the two domains. The catalysis of serine β-lactamase proceeds via acylation and deacylation
reactions. The three dimensional structure of metallo-β-lactamases displayed a common four layer
“αβ/βα” motif, with a central “ββ”- sandwich by Zn2+ ion(s), and two α-helices are located on the either
side. The active site of metallo-β-lactamases contain either 1 or 2 Zn2+ ions, which is coordinated to
metal ligating amino acids and polarized water molecule(s) necessary for the hydrolysis of β-lactam antibiotics.
Keeping the above views in mind, in this review we have shed light on the current knowledge
of the structures and mechanisms of catalysis of serine and metallo-β-lactamases. Moreover, mutational
studies on β-lactamases highlight the importance of the active site residues and residues in the vicinity to
the active site pocket in the catalysis. To combat bacterial infections more effeciently novel inhibitors of
β-lactamase in combination with antibiotics have been used which also form the theme of the review.
Keywords: Serine-β-lactamase, metallo-β-lactamase, β-lactam antibiotics, acylation reaction, deacylation reaction, structure of
β-lactamases, catalytic mechanism of β-lactamases, inhibitors of β-lactamases.
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