Val-237 for Ala substitution in the TEM-2 beta-lactamase dramatically alters the catalytic efficiencies towards carbenicillin and ticarcillin
| Autor: | Jean Peduzzi, Gilles Moreau, M. Barthelemy, G. Paul, David Alun Rowlands, Roger Labia |
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| Rok vydání: | 1994 |
| Předmět: |
Stereochemistry
Mutant Molecular Sequence Data Biology Microbiology beta-Lactamases Structure-Activity Relationship polycyclic compounds Genetics medicine Ticarcillin Amino Acid Sequence Molecular Biology Peptide sequence chemistry.chemical_classification Edman degradation biochemical phenomena metabolism and nutrition Carbenicillin Penicillin Kinetics Enzyme chemistry Carfecillin Mutation bacteria medicine.drug |
| Zdroj: | FEMS microbiology letters. 117(3) |
| ISSN: | 0378-1097 |
| Popis: | The mutant 554 of TEM-2 beta-lactamase was selected for a decrease in the resistance to carbenicillin of an Escherichia coli K12 carrier. The amino acid sequence of the mutant beta-lactamase was determined by manual Edman degradation analysis of proteolytic peptides. A single substitution Val for Ala was localized at position 237. The mutant exhibited only 2% of the catalytic efficiency of the wild-type enzyme towards carbenicillin and ticarcillin, whereas it retained 30-60% of the hydrolytic activity towards other penicillin and cephalosporin substrates. Carfecillin, the phenyl ester of the side-chain carboxyl group of carbenicillin, was hydrolysed as a good substrate. This suggests that the behaviour of the mutant enzyme towards carbenicillin may result from ionic rather than steric constraints. A molecular model of the Val-237 TEM-2 mutant suggests possible electrostatic interaction between Glu-171 and the carboxylic group of the side chain of carbenicillin. |
| Databáze: | OpenAIRE |
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