Sk. Dubois et al., TEM-DERIVED AND SHV-DERIVED EXTENDED-SPECTRUM BETA-LACTAMASES - RELATIONSHIP BETWEEN SELECTION, STRUCTURE AND FUNCTION, Journal of antimicrobial chemotherapy, 35(1), 1995, pp. 7-22
The later-generation cephalosporins were developed to overcome beta-la
ctamases which conferred resistance to earlier beta-lactam drugs. With
in two years of their clinical introduction, the ubiquitous TEM and SH
V plasmid-encoded beta-lactamase genes underwent simple point mutation
s that changed key amino acids around the active site of the protein a
nd enabled the enzyme to bind and hydrolyse these new drugs. Successiv
e mutations interacted in concert, radically increasing the enzymes' a
bilities to bind and confer resistance to later-generation cephalospor
ins. These modified enzymes have been classified in three groups, base
d on activity, and altered functions have been correlated with changes
in the enzyme structure.