Zhipeng Yu1,2, Ruotong Kan1, Sijia Wu1, Hui Guo1, Wenzhu Zhao1, Long Ding3, Fuping Zheng2, Jingbo Liu4. 1. College of Food Science and Engineering, Bohai University, Jinzhou, P.R. China. 2. Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, P.R. China. 3. College of Food Science and Engineering, Northwest A&F University, Yangling, P.R. China. 4. Laboratory of Nutrition and Functional Food, Jilin University, Changchun, P.R. China.
Abstract
BACKGROUND: There has been growing interest in the use of xanthine oxidase (XO) as a therapeutic agent to prevent gout and hyperuricemia. In the present study, XO inhibitory peptides were identified from tuna protein by virtual screening, and molecular docking was used to elicit the interaction mechanism between XO and peptides. RESULTS: A novel tetrapeptide, EEAK, exhibited high XO inhibitory activity with an IC50 of 173.00 ± 0.06 μM. Molecular docking analysis revealed that EEAK bound with the pivotal residues of XO's active sites (i.e., Glu802, Arg880, Glu1261) through two conventional hydrogen bond interactions, two attractive charge interactions, and one salt bridge. EEAK could also bind with the residues Phe649, Leu648, Lys771, Ser876, Phe914, and Thr1010 of XO. CONCLUSION: This study suggested that conventional hydrogen bond interactions and electrostatic interactions play an important role in XO inhibition. The novel XO inhibitory peptide EEAK from tuna protein could be used as potential candidate for controlling gout and hyperuricemia.
BACKGROUND: There has been growing interest in the use of xanthine oxidase (XO) as a therapeutic agent to prevent gout and hyperuricemia. In the present study, XO inhibitory peptides were identified from tuna protein by virtual screening, and molecular docking was used to elicit the interaction mechanism between XO and peptides. RESULTS: A novel tetrapeptide, EEAK, exhibited high XO inhibitory activity with an IC50 of 173.00 ± 0.06 μM. Molecular docking analysis revealed that EEAK bound with the pivotal residues of XO's active sites (i.e., Glu802, Arg880, Glu1261) through two conventional hydrogen bond interactions, two attractive charge interactions, and one salt bridge. EEAK could also bind with the residues Phe649, Leu648, Lys771, Ser876, Phe914, and Thr1010 of XO. CONCLUSION: This study suggested that conventional hydrogen bond interactions and electrostatic interactions play an important role in XO inhibition. The novel XO inhibitory peptide EEAK from tuna protein could be used as potential candidate for controlling gout and hyperuricemia.