Abstract
The X-ray crystal structure of the molecular complex of penicillin G with a deacylation-defective mutant of the RTEM-1 β-lactamase from Escherichia coli shows how these antibiotics are recognized and destroyed. Penicillin G is covalently bound to Ser 70 Oγ as an acyl-enzyme intermediate. The deduced catalytic mechanism uses Ser 70 Oγ as the attacking nucleophile during acylation. Lys 73 Nζ acts as a general base in abstracting a proton from Ser 70 and transferring it to the thiazolidine ring nitrogen atom via Ser 130 Oγ. Deacylation is accomplished by nucleophilic attack on the penicilloyl carbonyl carbon by a water molecule assisted by the general base, Glu 166.
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Strynadka, N., Adachi, H., Jensen, S. et al. Molecular structure of the acyl-enzyme intermediate in β-lactam hydrolysis at 1.7 Å resolution. Nature 359, 700–705 (1992). https://doi.org/10.1038/359700a0
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DOI: https://doi.org/10.1038/359700a0
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