New Mechanism for Inhibiting Carbonic Anhydrase with Bithionol
Author Information
Author(s): Roberto Paciotti, Simone Carradori, Andreas Angeli, Ilaria D'Agostino, Marta Ferraroni, Cecilia Coletti, Claudiu T. Supuran
Primary Institution: Department of Pharmacy “G. d'Annunzio” University of Chieti‐Pescara
Hypothesis
Bithionol's halogen atoms and hydroxyl groups can interact with carbonic anhydrase enzymes to inhibit their activity.
Conclusion
Bithionol shows micromolar inhibition of human carbonic anhydrase II through a unique halogen-bonding interaction with the His64 residue.
Supporting Evidence
- Bithionol showed a micromolar inhibition of specific human carbonic anhydrases.
- X-ray crystallography revealed a halogen-bond interaction between bithionol and His64 in hCA II.
- Quantum mechanics calculations estimated the strength of the halogen bond to be approximately 2.9 kcal/mol.
- Bithionol was inactive against hCA III due to mutations that prevent halogen bonding.
Takeaway
Bithionol is a small molecule that can stop certain enzymes in our body from working by using a special bond with a part of the enzyme.
Methodology
Bithionol was tested on human carbonic anhydrases using stopped-flow techniques and X-ray crystallography to study its binding interactions.
Limitations
Bithionol is a weak inhibitor with low selectivity over other carbonic anhydrases.
Digital Object Identifier (DOI)
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