Effects of isorhamnetin on tyrosinase: inhibition kinetics and computational simulation.
We studied the inhibitory effects of isorhamnetin on mushroom tyrosinase by inhibition kinetics and computational simulation. Isorhamnetin reversibly inhibited tyrosinase in a mixed-type manner at Ki=0.235±0.013 mM. Measurements of intrinsic and 1-anilinonaphthalene-8-sulfonate(ANS)-binding fluorescence showed that isorhamnetin did not induce significant changes in the tertiary structure of tyrosinase. To gain insight into the inactivation process, the kinetics were computed via time-interval measurements and continuous substrate reactions. The results indicated that inactivation induced by isorhamnetin was a first-order reaction with biphasic processes. To gain further insight, we simulated docking between tyrosinase and isorhamnetin. Simulation was successful (binding energies for Dock6.3: -32.58 kcal/mol, for AutoDock4.2: -5.66 kcal/mol, and for Fred2.2: -48.86 kcal/mol), suggesting that isorhamnetin interacts with several residues, such as HIS244 and MET280. This strategy of predicting tyrosinase interaction in combination with kinetics based on a flavanone compound might prove useful in screening for potential natural tyrosinase inhibitors.
College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, PR China.
Yue-Xiu
YX
Si
Zhi-Jiang
ZJ
Wang
Daeui
D
Park
Hyoung Oh
HO
Jeong
Sen
S
Ye
Hae Young
HY
Chung
Jun-Mo
JM
Yang
Shang-Jun
SJ
Yin
Guo-Ying
GY
Qian
D000363:Agaricales / Q000737:chemistry / Q000201:enzymology; D000817:Anilino Naphthalenesulfonates; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005456:Fluorescent Dyes; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D007700:Kinetics; D007980:Levodopa / Q000737:chemistry* / Q000378:metabolism; D008715:Methionine / Q000737:chemistry; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry; D013816:Thermodynamics
D000817:Anilino Naphthalenesulfonates; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D005656:Fungal Proteins; C047368:3-methylquercetin; D007980:Levodopa; D006639:Histidine; C027132:1-anilino-8-naphthalenesulfonate; D011794:Quercetin; D008715:Methionine; D014442:Monophenol Monooxygenase