Effects of Ser130Gly and Asp240Lys substitutions in extended-spectrum beta-lactamase CTX-M-9

Abstract

In CTX-M-9 extended-spectrum beta-lactamases (ESBLs), an S130G mutation induced a 40- to 650-fold increase in 50% inhibitory concentrations but decreased hydrolytic activity against cefotaxime. A D240K mutation did not modify enzymatic efficiency against ceftazidime. Residue K240 could interact with Q270 and therefore not with ceftazidime, in contrast with what was observed with certain TEM/SHV-type ESBLs.

FIG. 1.

Structures of CTX-M-9 (A), the D240K mutant (B), and CTX-M-16 (C) obtained by molecular modeling and the crystallographic structure of TEM-1 (D) (17). Two black dots indicate the positions of water molecules: W1, the catalytic water molecule maintained by the lateral chains of residues 166, 170, and 70, and W2, the water molecule of oxyanionic hole formed by the main chains of residues 70 and 237. The hydrogen bonds between residues 170, 240, and 270 are indicated by dashed lines.