OLURANTI ESTHER OLAIYA, ADEJOKE NAOMI KOLAWOLE, A.O. KOLAWOLE#
Biomolecular Structure and Dynamics Unit, Department of Biochemistry, The Federal University of Technology, Akure, Nigeria
The interaction between metronidazole and some vital proteins, which exaggerates the reported toxicity of the drug, is uncertain. Herein, the molecular interaction between aldehyde dehydrogenase (ALDH), a major detoxifying enzyme with pathophysiological implications, and metronidazole was investigated by spectroscopy techniques. Spectrofluorimetric measurements revealed that metronidazole quenched the ALDH intrinsic fluorescence through a non-fluorescent ALDH-metronidazole complex. Dynamic quenching and non-radiative energy transfer were responsible for the bathochromic fluorescence quenching. Thermodynamic analysis showed that metronidazole binds to ALDH via hydrogen and van der Waals interactions. The association was not spontaneous but enough to cause perturbation of the protein structure. The enzyme has approximately two association sites for metronidazole, non-cooperative binding, with a binding constant (Ka) of 5.8×103 L·M–1. The association of the complex was favorable compared to its dissociation at temperatures and pH studied. The fluorescence emission quenching obeys FRET phenomenon with a R = 3.42 nm. ALDH as nano-particles in a drug delivery of metronidazole for detoxification is hereby suggested.
Key words: Aldehyde dehydrogenases, fluorescence quenching metronidazole, spectroscopy.
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