Ligand recognition by chloroperoxidase using molecular interaction fields and quantum chemistry calculations

Abstract

We recently reported that chloroperoxidase (CPO) from Caldariomyces fumago showed atypical kinetic behavior for the oxidation of 4,6 dimethyl dibenzothiophene (DMDBT). In this work, we undertake the theoretical study of DMDBT docking into CPO's active site, in order to clarify its binding capacity and affinity using molecular interaction fields and quantum mechanical procedure. The results revealed that CPO has two substrate binding sites with similar affinities for DMDBT. This finding suggests that the atypical kinetic behavior of CPO for the oxidation of DMDBT might be due to the simultaneous binding of two DMDBT molecules during its reaction cycle. Finally, we extend these results to carbazole, a nitrogen-containing PAH, through experimental and theoretical studies.

Keywords:

• Chloroperoxidase
• Ligand docking
• Sigmoidal kinetics
• π–π Dimers

Acknowledgements

This work was supported by grants from the Mexican Petroleum Institute (D.000344 and D.000293), CONACYT and COFAA-SIP/IPN. We acknowledge Dr Marcela Ayala from IBT (UNAM) for fruitful discussions.