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A four-membered cyclic amide. Hydrolytic opening of this ring is a major mechanism by which beta-lactamases inactivate susceptible antibiotics.

A beta-lactam antibiotic with bulky substituents whose susceptibility to hydrolysis depends on the particular beta-lactamase.

An appropriately positioned general base helps remove the proton from the serine residue hydroxyl, increasing its nucleophilicity. A lysine residue, such as Lys73 in the class A beta-lactamase catalytic network, is a plausible participant; its protonation state depends on its active-site environment and interactions with other residues. A glutamate residue, notably Glu166, also participates in proton transfer and activation of the water needed for deacylation. Efficient catalysis requires proton-transfer chemistry as well as positioning the attacking oxygen. The precise division of roles during acylation depends on the enzyme state, so the drawing alone cannot assign a complete mechanism to one residue.^[ref]

A beta-lactam antibiotic used as a substrate in comparisons of beta-lactamase kinetics.

A reference TEM-family class A beta-lactamase against which altered-spectrum variants can be compared.

A TEM-family beta-lactamase variant whose structure and substrate specificity differ from TEM-1. Controlled comparisons distinguish access remodeling, catalytic behavior and altered expression.^[ref]