The Effect of Histidine Residue Modification on Tyrosinase Activity and Conformation: Inhibition Kinetics and Computational Prediction
2008; Taylor & Francis; Volume: 26; Issue: 3 Linguagem: Inglês
10.1080/07391102.2008.10507254
ISSN1538-0254
AutoresLin Gou, Zhi-Rong Lü, Daeui Park, Sang Ho Oh, Long Shi, Seong Jin Park, Jong Bhak, Yong‐Doo Park, Zhen-Long Ren, Fei Zou,
Tópico(s)RNA and protein synthesis mechanisms
ResumoAbstract We found that the histidine chemical modification of tyrosinase conspicuously inactivated enzyme activity. The substrate reactions with diethylpyridinecarbamate showed slow-binding inhibition kinetics (K I = 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. Key words: TyrosinaseHistidine modificationInhibition kineticsStructure predictionDocking simulation
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