- Discovery of inhibitors that are promising when acting with antibiotics.
- Opportunity to create library of inhibitors based on changing substituents on the boronic inhibitors.
- These inhibitors do not resemble beta-lactams: high affinity binding is promising to see. 
- ID of key residues that are important for ideal interactions for inhibitors.


Grand Valley State University

- From identifying the X-ray Crystal structure of the beta-lactamase (ADC-7), boronic acid transition state inhibitors (BATSIs) were tested – these are inhibitors with a basis for inhibition properties against ADC-7. 
- They do not have the beta-lactam ring.

Boronic acid transition state inhibitors

Powers, R. A., Swanson, H. C., Taracila, M. A., Florek, N. W., Romagnoli, C., Caselli, E., Prati, F., Bonomo, R. A., & Wallar, B. J. (2014). Biochemical and Structural Analysis of Inhibitors Targeting the ADC-7 Cephalosporinase of Acinetobacter baumannii. Biochemistry, 53(48), 7670–7679. https://doi.org/10.1021/bi500887n

Biochemical and Structural Analysis of Inhibitors Targeting the ADC‑7 Cephalosporinase of Acinetobacter baumannii

- Both Boronic inhibitors tested were effective in inhibiting ADC-7. 
- When tested with ADC-7 expressing bacteria, they observed excellent inhibition of ADC-7 when combined with beta-lactam antibiotics. 


Potential Inhibitors of Beta-Lactamases 

- Position of the R1 side chain is similar to that how beta-lactam antibiotics bind 
- Key residues were identified that are indicative of key binding areas the beta-lactam antibiotics bind.
- Variability was observed in the R2 region, they did not fully explain the importance of the R2 side-chain. However, they discovered an important residue (Arg340) that could be important in the binding of inhibitors to the beta-lactamase enzyme, ADC-7. 
- Both inhibitors were successful in binding the ADC-7.


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