The effect of histidine residue modification on tyrosinase activity and conformation: inhibition kinetics and computational prediction.
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.
Guo
Lin
L
College of Life Science and State Key Laboratory for Plant Genetics and Breeding, Sichuan Agricultural University, Sichuan 625014, PR China.
Lu
Zhi-Rong
ZR
Park
Daeui
D
Oh
Sang Ho
SH
Shi
Long
L
Park
Seong Jin
SJ
Bhak
Jong
J
Park
Yong-Doo
YD
Ren
Zhen-Long
ZL
Zou
Fei
F
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
D000085:Acetates; D006639:Histidine; C016274:bromoacetate; D014442:Monophenol Monooxygenase