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3350211 
Journal Article 
Non-specific binding sites help to explain mixed inhibition in mushroom tyrosinase activities 
Hassani, S; Haghbeen, K; Fazli, M 
2016 
Yes 
European Journal of Medicinal Chemistry
ISSN: 0223-5234
EISSN: 1768-3254 
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER 
ISSY-LES-MOULINEAUX 
122 
138-148 
English 
27344491 
WOS:000383003900012 
is supplemented by 3484807 - Supplementary material
Inhibition and activation studies of tyrosinase could prove beneficial to agricultural, food, cosmetic, and pharmaceutical industries. Although non-competitive and mixed-inhibition are frequent modes observed in kinetics studies on mushroom tyrosinase (MT) activities, the phenomena are left unexplained. In this study, dual effects of phthalic acid (PA) and cinnamic acid (CA) on MT during mono-phenolase activity were demonstrated. PA activated and inhibited MT at concentrations lower and higher than 150 μM, respectively. In contrast, CA inhibited and activated MT at concentrations lower and higher than 5 μM. The mode of inhibition for both effectors was mixed-type. Complex kinetics of MT in the presence of a modulator could partly be ascribed to its mixed-cooperativity. However, to explain mixed-inhibition mode, it is necessary to demonstrate how the ternary complex of substrate/enzyme/effector is formed. Therefore, we looked for possible non-specific binding sites using MT tropolone-bound PDB (2Y9X) in the computational studies. When tropolone was in MTPa (active site), PA and CA occupied different pockets (named MTPb and MTPc, respectively). The close Moldock scores of PA binding posed in MTPb and MTPa suggested that MTPb could be a secondary binding site for PA. Similar results were obtained for CA. Ensuing results from 10 ns molecular dynamics simulations for 2Y9X-effector complexes indicated that the structures were gradually stabilized during simulation. Tunnel analysis by using CAVER Analyst and CHEXVIS resulted in identifying two distinct channels that assumingly participate in exchanging the effectors when the direct channel to MTPa is not accessible. 
IRIS
• Dibutyl Phthalate (DBP)
     Database Searches
          Litsearch Jan 2016 - July 2016
               Pubmed
     Excluded: No Primary Data on Health Effects
          Not chemical specific