title: The effect of histidine residue modification on tyrosinase activity and conformation: inhibition kinetics and computational prediction.
abstract: We found that the histidine chemical modification of tyrosinase conspicuously inactivated enzyme activity. The substrate reactions with diethylpyridinecarbamate showed slow-binding inhibition kinetics (KI = 0.24 +/- 0.03 mM). Bromoacetate, as another histidine modifier, was also applied in order to study inhibition kinetics. The bromoacetate directly induced the exposures of hydrophobic surfaces following by complete inactivation via ligand binding. For further insights, we predicted the 3D structure of tyrosinase and simulated the docking between tyrosinase and diethylpyridinecarbamate. The docking simulation was shown to the significant binding energy scores (-3.77 kcal/mol by AutoDock4 and -25.26 kcal/mol by Dock6). The computational prediction was informative to elucidate the role of free histidine residues at the active site, which are related to substrate accessibility during tyrosinase catalysis.
authors.affiliation: College of Life Science and State Key Laboratory for Plant Genetics and Breeding, Sichuan Agricultural University, Sichuan 625014, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Lu
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Oh
authors.forename: Long
authors.initials: L
authors.lastname: Shi
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Jong
authors.initials: J
authors.lastname: Bhak
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
authors.forename: Zhen-Long
authors.initials: ZL
authors.lastname: Ren
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
mesh_terms: D000085:Acetates / Q000737:chemistry; D000363:Agaricales / Q000201:enzymology; D000818:Animals; D006639:Histidine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D000085:Acetates; D006639:Histidine; C016274:bromoacetate; D014442:Monophenol Monooxygenase