Inhibitory effects of cefotaxime on the activity of mushroom tyrosinase.
Tyrosinase (EC 1.14.18.1) catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones that form brown or black pigments. In the present paper, cefotaxime, a cephalosporin antibacterial drug, was tested as an inhibitor of tyrosinase. The results show that cefotaxime inhibits both the monophenolase and diphenolase activities of tyrosinase. For the monophenolase activity, cefotaxime increased the lag time and decreased the steady-state activity with an IC50 of 3.2 mM. For the diphenolase activity, the inhibition by cefotaxime is reversible and mix-I type with an IC50 of 0.14 mM. The inhibition constants (K(I) and K(IS)) were determined to be 0.14 and 0.36 mM, respectively. The molecular mechanism of inhibition of tyrosinase by cefotaxime was determined by fluorescence quenching and molecular docking. The results demonstrated that cefotaxime was a static quencher of tyrosinase and that cefotaxime could dock favorably in the active site of tyrosinase. This research may offer a lead for designing and synthesizing novel and effective tyrosinase inhibitors in the future.
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, Xiamen 361102, China.
Yong-Hua
YH
Hu
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen 361102, China.
Jiang-Xing
JX
Zhuang
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, Xiamen 361102, China.
Feng
F
Yu
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, Xiamen 361102, China.
Yi
Y
Cui
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, Xiamen 361102, China.
Wen-Wen
WW
Yu
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, Xiamen 361102, China.
Chong-Ling
CL
Yan
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, Xiamen 361102, China; Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen 361005, China. Electronic address: chenqx@xmu.edu.cn.
Qing-Xi
QX
Chen
D000363:Agaricales / Q000201:enzymology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D055162:Biocatalysis / Q000187:drug effects; D020134:Catalytic Domain; D002439:Cefotaxime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005453:Fluorescence; D020128:Inhibitory Concentration 50; D007700:Kinetics; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D014443:Tyrosine; D010088:Oxidoreductases; C412191:monophenolase; D014442:Monophenol Monooxygenase; D002439:Cefotaxime
Cefotaxime; Docking; Fluorescence quenching; Inhibition; Tyrosinase