Clavulanic acid (Fig. P22.98) is an inhibitor of b-lactamase enzymes, which cause penicillin resistance.

Clavulanic acid inhibits b-lactamases by first reacting with the side-chain hydroxy group of an active-site serine residue (abbreviated as shown in Fig. P22.98). The resulting derivative A then reacts with the side-chain amino group of a lysine residue in the same active site to give the product B, which permanently blocks the active site, along with a by-product C, which is released into solution. Assuming acids and bases are present as needed, provide curved-arrow mechanisms for these reactions, and draw a structure of by-product C.

Transcribed Image Text:

E-OH + from a serine residue of the enzyme H Figure P22.98 clavulanic acid (conjugate base) A + E-NH₂ from a lysine residue of the enzyme OH E B E [1] H H CO, CH A NH-E + C OH