1st International Conference on Chemo and BioInformatics, ICCBIKG 2021, (292)
AUTHOR(S) / АУТОР(И): Ilija Cvijetić, Petar Ristivojević, Maja Krstić-Ristivojević, Dušanka Milojković-Opsenica,
E-ADRESS / Е-АДРЕСА: email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org
ABSTRACT / САЖЕТАК:
Tyrosinase is an enzyme involved in generation of dopamine-quinones, which has an important role in oxidative stress associated with the Parkinson’s disease. It is also a common molecular target for the design of novel anti-melanogenic agents. The inhibition of tyrosinase might be responsible for the experimentally observed intracellular antioxidant activity of α-arbutin. Moreover, intrinsic radical scavenging capacity of α-arbutin should also be considered.
The binding mode of α-arbutin into the active site of Bacillus megaterium tyrosinase is predicted using AutoDock Vina 1.1. To map the thermodynamic feasibility of HAT and SET-PT mechanisms of the intrinsic antioxidant capacity α-arbutin, bond dissociation enthalpies (BDEs) and ionization potential (IP) are calculated using DFT with B3LYP functional and 6-31+g(d,p) basis set. α-Arbutin fitted well into the active site of tyrosinase, with the calculated binding affinity of -17.5 kcal/mol. The phenolic moiety is located deep into the binding pocket, interacting with His residues around Cu2+ ion. The binding mode of α-arbutin is stabilized via HBD interactions with His231, His42, His60, Arg209, Gly216, and Asn205, HBA interaction with Arg209 at the outer part of active site, and hydrophobic interactions with His208, Val218 and Ala221. The calculated IP of
α-arbutin is 175.18 kcal/mol, and BDE of phenolic group is 79.85 kcal/mol. The spin densities of radical-cation and hydroxyl radical are delocalized on the aglycone moiety. The results of this study provide valuable structural insights into the molecular mechanisms of biological action of α-arbutin, and might be exploited for the design of more potent analogues.
KEY WORDS / КЉУЧНЕ РЕЧИ:
α-arbutin, tyrosinase, antioxidant activity, molecular docking, DFT
REFERENCES / ЛИТЕРАТУРА:
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