Kinetics for zinc ion induced sepia pharaonis arginine kinase inactivation and aggregation

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Kinetics for zinc ion induced sepia pharaonis arginine kinase inactivation and aggregation
Y X Si; Jinhyuk Lee; J G Cheng; S J Yin; Y D Park; G Y Qian; X M Jiang
Bibliographic Citation
Protein and Peptide Letters, vol. 23, no. 6, pp. 508-517
Publication Year
Arginine kinase is an essential enzyme which is closely related to energy metabolism in marine invertebrates. Arginine kinase provides a significant role in quick response to environmental change and stress. In this study, we simulated a tertiary structure of Sepia pharaonis arginine kinase (SPAK) based on the gene sequence and conducted the molecular dynamics simulations between SPAK and Zn2+. Using these results, the Zn2+ binding sites were predicted and the initial effect of Zn2+ on the SPAK structure was elucidated. Subsequently, the experimental kinetic results were compared with the simulation results. Zn2+ markedly inhibited the activity of SPAK in a manner of non-competitive inhibitions for both arginine and ATP. We also found that Zn2+ binding to SPAK resulted in tertiary conformational change accompanying with the hydrophobic residues exposure. These changes caused SPAK aggregation directly. We screened two protectants, glycine and proline, which effectively prevented SPAK aggregation and recovered the structure and activity. Overall, our study suggested the inhibitory effect of Zn2+ on SPAK and Zn2+ can trigger SPAK aggregation after exposing large extent of hydrophobic surface. The protective effects of glycine and proline against Zn2+ on SPAK folding were also demonstrated
AggregationArginine kinaseInhibitionMolecular dynamics simulationSepia pharaonisZn2+
Bentham Science Publ Ltd
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Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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