Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 22, Issue 49, Pages 17704-17714Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201602762
Keywords
antibiotic resistance; imipenemase; beta-lactam antibiotics; metalloenzyme; metallo-beta-lactamase
Categories
Funding
- NHMRC [APP1084778]
- Australian Research Council [DP150104358]
- Future Fellowships [FT120100694, FT120100421]
- University of Queensland
- Science Foundation Ireland
- National Science Foundation (USA) [CHE1303852, CHE0820965]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1303852] Funding Source: National Science Foundation
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Antibiotic resistance has emerged as a major threat to global health care. This is largely due to the fact that many pathogens have developed strategies to acquire resistance to antibiotics. Metallo-beta-lactamases (MBL) have evolved to inactivate most of the commonly used beta-lactam antibiotics. AIM-1 is one of only a few MBLs from the B3 subgroup that is encoded on a mobile genetic element in a major human pathogen. Here, its mechanism of action was characterised with a combination of spectroscopic and kinetic techniques and compared to that of other MBLs. Unlike other MBLs it appears that AIM-1 has two avenues available for the turnover of the substrate nitrocefin, distinguished by the identity of the rate-limiting step. This observation may be relevant with respect to inhibitor design for this group of enzymes as it demonstrates that at least some MBLs are very flexible in terms of interactions with substrates and possibly inhibitors.
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