| Autor: |
Nichole K, Stewart, Marta, Toth, Anastasiya, Stasyuk, Mijoon, Lee, Clyde A, Smith, Sergei B, Vakulenko |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
ACS Infect Dis |
| ISSN: |
2373-8227 |
| Popis: |
Avibactam is a potent diazobicyclooctane inhibitor of class A and C β-lactamases. The inhibitor also exhibits variable activity against some class D enzymes from Gram-negative bacteria; however, its interaction with recently discovered class D β-lactamases from Gram-positive bacteria has not been studied. Here, we describe microbiological, kinetic, and mass spectrometry studies of the interaction of avibactam with CDD-1, a class D β-lactamase from the clinically important pathogen Clostridioides difficile, and show that avibactam is a potent irreversible mechanism-based inhibitor of the enzyme. X-ray crystallographic studies at three time-points demonstrate the rapid formation of a stable CDD-1-avibactam acyl–enzyme complex and highlight differences in the anchoring of the inhibitor by class D enzymes from Gram-positive and Gram-negative bacteria. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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