Molecular docking insights into the inhibition of laccase activity by medicarpin

Abstract

Molecular docking calculations were performed to understand the inhibition mechanism of medicarpin on the lignin degradation enzyme laccase. The study was carried out in two stages. The first stage was performed on a laccase–oligolignol complex, to elucidate the active binding mode in the enzyme that initiates lignin degradation. The second stage was performed on a laccase–medicarpin complex, to understand the inhibitory effect of medicarpin on the enzymatic mechanism. In this two-step procedure, the crystal structure of a laccase (PDB: 1GYC) obtained from Trametes versicolor, a white-rot fungus capable of degrading lignin in wood, was employed because it produces considerable amounts of laccase. The results obtained from the laccase–oligolignol complex indicate that the binding site is located in a pocket that surrounds the T1 copper atom, which is in agreement with experimental reports. The results from the laccase–medicarpin complex indicate that the inhibitory effect occurs by the blockage of a solvent channel in the T. versicolor laccase by a medicarpin conformer, preventing the rapid access of molecular oxygen to the trinuclear T2/T3 copper cluster, and also by the coupling of medicarpin conformers in the T1 site pocket, blocking access by oligolignol molecules. Therefore, this coupling of medicarpin to two sites in laccase interrupts the enzymatic mechanism of lignin degradation. The results of this study may be useful in developing wood-preserving formulations based on medicarpin or similar molecular structures and in expanding the scientific knowledge of laccase activity for biotechnological applications.