title: In silico approach to inhibition of tyrosinase by ascorbic acid using molecular docking simulations.
abstract: Current evidence suggests that endogenous dopamine may act as a neurotoxin following its oxidation to an oquinone and reaction with cellular thiols, which are neutoxic, which may occur spontaneously or via reaction with tyrosinase or some other enzymes. Tyrosinase (E.C. 1.14.18.1) with two cupper ions coordinated by three histidines is a bifunctional enzyme that catalyses both the hydroxylation of tyrosine to L-DOPA and the consequent oxidation of the resulting catechol-containing species to an o-quinone. Therefore, tyrosinase may play a role in neuromelanin formation in the brain and could be central to dopamine neurotoxicity by contributing to the neurodegeneration associated with Parkinson's disease. In the present study, inhibitory effect of ascorbic acid against tyrosinase has been investigated and it has shown a remarkable inhibitory effect in in vitro assays. Then, the in silico-based experiments established through molecular docking calculations and scoring, docking search algorithm, and data plotting indicated that ascorbic acid is strong inhibitor of tyrosinase by interacting with four amino acid units (histidine 263, serine 282, phenylalanine 264, and valin 283) in the active site of the enzyme. The compound also had two long distant hydrogen bindings with Cu1 and Cu2 with distances of 3.57 and 3.41 A, respectively, through its O5 atom.
authors.forename: F Sezer
authors.initials: FS
authors.lastname: Senol
authors.forename: M Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.forename: Gurdal
authors.initials: G
authors.lastname: Orhan
authors.forename: Erdem
authors.initials: E
authors.lastname: Gurkas
authors.forename: Ilkay Erdogan
authors.initials: IE
authors.lastname: Orhan
authors.forename: Nese Subutay
authors.initials: NS
authors.lastname: Oztekin
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey. iorhan@gazi.edu.tr.
authors.forename: Fikri
authors.initials: F
authors.lastname: Ak
mesh_terms: D000363:Agaricales / Q000201:enzymology; D001205:Ascorbic Acid / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D014442:Monophenol Monooxygenase; D001205:Ascorbic Acid