title: Mixed-type inhibition of tyrosinase from Agaricus bisporus by terephthalic acid: computational simulations and kinetics.
abstract: Tyrosinase inhibition studies are needed due to the agricultural and medicinal applications. For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics were important. We predicted the 3D structure of tyrosinase from Agaricus bisporus, used a docking algorithm to simulate binding between tyrosinase and terephthalic acid (TPA) and studied the reversible inhibition of tyrosinase by TPA. Simulation was successful (binding energies for Autodock4 = -1.54 and Fred2.0 = -3.19 kcal/mol), suggesting that TPA interacts with histidine residues that are known to bind with copper ions at the active site. TPA inhibited tyrosinase in a mixed-type manner with a K ( i ) = 11.01 ± 2.12 mM. Measurements of intrinsic and ANS-binding fluorescences showed that TPA induced no changes in tertiary structure. The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxyl groups and orientation may prove useful for screening of potential tyrosinase inhibitors.
authors.affiliation: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, 315100, P. R. China.
authors.forename: Shang-Jun
authors.initials: SJ
authors.lastname: Yin
authors.forename: Yue-Xiu
authors.initials: YX
authors.lastname: Si
authors.forename: Yong-Fu
authors.initials: YF
authors.lastname: Chen
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Qian
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Lü
authors.forename: Sangho
authors.initials: S
authors.lastname: Oh
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.forename: Sanghyuk
authors.initials: S
authors.lastname: Lee
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Dong-Youn
authors.initials: DY
authors.lastname: Lee
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
mesh_terms: D000364:Agaricus / Q000737:chemistry / Q000201:enzymology*; D000595:Amino Acid Sequence; D003198:Computer Simulation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D010795:Phthalic Acids / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D016166:Free Radical Scavengers; D010795:Phthalic Acids; C011363:terephthalic acid; D014442:Monophenol Monooxygenase