Homobrassinolide induced conformational changes in hexokinase: a possible mechanism for its antidiabetic potential

Abstract

Hormonal regulation of cell growth and development, tissue morphology, metabolism and physiological function in animals and man is a well-established knowledge domain in modern biological science. The present study was carried out to investigate the structural stability of hexokinase when exposed to diabetic levels of glucose and its binding efficiency. The fluorescence study indicated that 28-homobrassinolide was able to protect or restore the native structure of hexokinase. Proteins are synthesized and fold into the native form to become active. The inability of a protein molecule to remain in its native form is called as protein misfolding and this is because of several factors. Protein aggregation and misfolding are known to play a critical role in several human diseases including diabetes. Homobrassinolide interaction with hexokinase was studied by UV-Vis spectrophotometer and fluorescence spectrophotometer. Results were suggested that the denatured hexokinase was renatured upon binding with homobrassinolide. In silico, docking study was performed to recognize the binding activity of homobrassinolide against a subunit of the glucokinase, and homobrassinolide was able to bind to the drug binding pocket of glucokinase. The glide energy is -7.1 kcal/mol, suggesting the high binding affinity of homobrassinolide to glucokinase. Overall, these studies predict that the phytohormone 28-homobrassinolide would function as an anti-diabetic when present in human and animal diet by augmenting the hexokinase enzyme activity in the animal cell. Copyright © 2015 John Wiley & Sons, Ltd.