The replacement of the C3 carboxylate in phenoxymethylpenicillin by a hydroxymethyl group and of the C4 carboxylate in cephalosporins by both a lactone and an aldehyde gives derivatives which are still good substrates for Bacillus cereus 569/H β-lactamase I. The enzyme rate-enhancement factors for the hydrolysis of the modified β-lactams vary from 104 to 106. All three modified substrates show bell-shaped (k cat/Km)-pH profiles indicative of two catalytically important ionising residues on the protein of pKa about 5 and 9. Although lysine 234 is a highly conserved residue in class A β-lactamases and has been traditionally thought to interact with the carboxylate of the β-lactam antibiotic, it is not responsible for the decrease in enzyme activity at high pH corresponding to the pKa of about 9.
|Number of pages||5|
|Journal||Journal of the Chemical Society, Perkin Transactions 2|
|Publication status||Published - 1 Jan 1993|