Direct interaction of ONO-5046 with human neutrophil elastase through ¹H NMR and molecular docking

International Journal of Biological Macromolecules
Li FengYiming Li

Abstract

Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as pulmonary emphysema, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and other inflammatory diseases. Therefore, searching for appropriate and potential human neutrophil elastase inhibitors (HNEI) that would restore the balance between the free enzyme and the endogenous inhibitors would be of therapeutic interest. ONO-5046 is the first specific HNEI to improve respiratory function and protect lung tissues against various lung injuries. However, the mechanism of ONO-5046 to HNE is still unclear. In this study, the binding properties of ONO-5046 were investigated through (1)H NMR, molecular docking, and bioassay methods to understand the effect of ONO-5046 to HNE. The proton spin-lattice relaxation rate and molecular rotational correlation time results indicated that ONO-5046 has higher affinity with HNE. The molecular docking study showed that ONO-5046 is perfectly matched for the primary enzyme specificity pocket (S1 pocket), and is tightly bound to this pocket of HNE through hydrophobic and hydrogen bonding interactions. The results of both methods were validated through analysis of the HNE i...Continue Reading

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Citations

Jul 21, 2015·The Journal of Clinical Investigation·Ramesh C NayakJose A Cancelas
Mar 25, 2014·Experimental and Therapeutic Medicine·Ting Zhang, Xiangdong Zhou
Mar 6, 2019·Journal of Asian Natural Products Research·Guo-Li HuangYe-Gao Chen
Oct 10, 2020·Frontiers in Chemistry·Letizia CrocettiMark T Quinn
Jul 24, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Aditya RayasamZinaida S Vexler

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