Glycation induced conformational alterations in caprine brain cystatin (CBC) leads to aggregation via passage through a partially folded state

Khaki, P.S.S. and Feroz, A. and Siddiqui, A.A. and Qadri, S.M. and Amin, F. and Bano, B. (2018) Glycation induced conformational alterations in caprine brain cystatin (CBC) leads to aggregation via passage through a partially folded state. International Journal of Biological Macromolecules, 106. pp. 917-929. ISSN 1418130

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Abstract

Glycation induced advanced glycation end products (AGEs) of proteins formed as a result of Maillard reaction is currently at the heart of a number of pathological conditions. The formation of chemically stable AGEs can permanently alter protein structure and function; hence can serve as an implication in long term complications. Cystatins with high amyloidogenic inclination are implicated in various diseases including cancer and neurodegenerative conditions. The aggregates of cystatin purified from caprine brain have been studied on addition of glucose and ribose using UV absorption, fluorescence emission, circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). In the present study AGEs have been monitored and characterized. CBC was incubated for varying time intervals up to 41 days in the presence of 17 and 100 mM each of glucose and ribose. Ribose at both the concentrations was found to be more potent glycating agent as compared to glucose at these concentrations which is evident from UV and fluorescence spectroscopic studies. Altered intrinsic and high ANS fluorescence for 100 mM and 17 mM sugar concentrations respectively, suggested the existence of molten globule state of CBC. Glycated CBC as AGEs and aggregates were observed on day 27 and 41 respectively. Formation of AGEs was confirmed by employing AGEs specific fluorescence studies. CBC aggregates confirmed the presence of β-sheet structure as shown by far-UV CD, dye binding assay and transmission electron microscopy (TEM). Current study is of immense importance as cystatin is a potential candidate of amyloidogenic tendency and a potent endogenous regulator of thiol proteases; hence serves to be an attractive model to study amyloidogenesis of brain cysteine protease inhibitor.

Item Type: Article
Uncontrolled Keywords: Advanced glycation end products (AGEs); ANS fluorescence; Caprine brain cystatin (CBC); Molten globule; Spectroscopy
Divisions: Faculties > Faculty of Life Sciences > Department of Biochemistry
Depositing User: AMU Library
Date Deposited: 20 Jan 2018 04:03
Last Modified: 20 Jan 2018 04:03
URI: http://ir.amu.ac.in/id/eprint/10844

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