IMR Press / FBL / Volume 24 / Issue 6 / DOI: 10.2741/4765

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Characterization of structural requirement for binding of gigantol and aldose reductase
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1 School of Basic Medical Sciences,Guangzhou University of Chinese Medicine, Guangzhou Guangdong,510006, PR China
2 School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310000, PR China
Front. Biosci. (Landmark Ed) 2019, 24(6), 1024–1036; https://doi.org/10.2741/4765
Published: 1 March 2019
(This article belongs to the Special Issue Leader sequences of coronavirus are altered during infection)
Abstract

We previously reported that gigantol extracted from Caulis Dendrobii has significant therapeutic benefits for the treatment of galactosemic cataracts through its ability to inhibit aldose reductase (AR) activity. In this study, we identified the binding sites and structurally characterized the interaction between gigantol and AR, to understand the mechanism (s) of the effects of gigantol on cataracts. Gigantol was found to be protective against diabetic cataracts (DC) in rats induced by streptozotocin. Molecular docking predicted the binding sites between AR and gigantol to be residues Trp111, His110, Tyr48 and Trp20. Mutation of each of these residues led to a significant reduction in AR activity. Cold-spray ionization mass spectrometry measurements showed that the binding of gigantol to AR is concentration-dependent and that the maximum stoichiometric ratio of non-covalent bonding is 1:24.4. pH and temperature did not influence the interaction. Taken together, we provide further mechanistic evidence of the beneficial effects of gigantol on DC.

Keywords
Binding Sites
Gigantol
Aldose Reductase
Diabetic Cataract
Site-Directed Mutagenesis
Cold-Spray Ionization Mass Spectrometry
Figures
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