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An aminopenicillin antibiotic acting on bacterial cell wall synthesis. Susceptibility can be altered by beta-lactamase activity and other mechanisms, separating target chemistry from whole-organism response.

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

A cephalosporin antibiotic in the beta-lactam family. Its substituents affect interactions with bacterial targets and resistance enzymes; susceptibility to beta-lactamase hydrolysis therefore depends on the particular enzyme rather than the family name alone.

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]

Researcher in enzyme structural biology. Langan and collaborators used neutron and X-ray crystallography to investigate a conserved glutamate in beta-lactamase, connecting atomic positions with a proposed catalytic role.^[ref]

A penicillin antibiotic, also called benzylpenicillin, that acts on bacterial cell wall synthesis. It is used as a reference substrate in some beta-lactamase measurements, separating an enzyme’s activity on one substrate from activity on the entire drug family.

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

It hydrolyses the beta-lactam ring of susceptible antibiotics, reducing their activity. Sequence variants can alter the substrate range, so improved performance against one compound need not imply a universal improvement against every beta-lactam. ^[ref]

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]