Effect of substitution of Asn for Arg-276 in the cefotaxime-hydrolyzing class A beta-lactamase CTX-M-4

FEMS Microbiol Lett. 1998 Dec 15;169(2):289-93. doi: 10.1111/j.1574-6968.1998.tb13331.x.


The effect of substitution of asparagine for arginine at position 276 (Ambler's numbering) on the properties of the extended-spectrum beta-lactamase CTX-M-4 was studied. Compared with CTX-M-4, the mutant beta-lactamase CTX-M-4(R276N) conferred lower levels of resistance to cefotaxime, ceftriaxone and aztreonam while the levels of resistance to penicillins and penicillin-inhibitor combinations were similar. Arg-276-->Asn substitution rendered CTX-M-4 slightly less susceptible to inhibition by clavulanate and tazobactam. It also caused a three-fold reduction in the relative rate of hydrolysis of cefotaxime. These results indicate that Arg-276 in CTX-M-type beta-lactamases may be implicated in hydrolysis of oxyimino-beta-lactams; they do not, however, support the hypothesis that Arg-276 is the functional equivalent of Arg-244 found in other class A beta-lactamases.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Substitution / genetics*
  • Arginine / chemistry*
  • Asparagine / chemistry*
  • Bacterial Proteins*
  • Cefotaxime / metabolism*
  • Cefotaxime / pharmacology
  • Cephalosporins / metabolism*
  • Cephalosporins / pharmacology
  • Drug Resistance, Microbial
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Mutagenesis
  • beta-Lactamase Inhibitors
  • beta-Lactamases / chemistry*


  • Bacterial Proteins
  • Cephalosporins
  • beta-Lactamase Inhibitors
  • Asparagine
  • Arginine
  • CTX-M-4 protein, Salmonella typhimurium
  • beta-Lactamases
  • Cefotaxime