Intra-molecular lysine-arginine derived advanced glycation end-product cross-linking in Type I collagen: A molecular dynamics simulation study.
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Date
2016-11
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Open Access funded by Biotechnology and Biological Sciences Research Council under a Creative Commons license
Abstract
Covalently cross-linked advanced glycation end products (AGE) are among the major post-translational modifications to proteins as a result of non-enzymatic glycation. The formation of AGEs has been shown to have adverse effects on the properties of the collagenous tissue; they are even linked to a number of age related disorders. Little is known about the sites at which these AGEs form or why certain sites within the collagen are energetically more favourable than others. In this study we have used a proven fully atomistic molecular dynamics approach to identify six sites where the formation of the intra-molecular 3-deoxyglucosone-derived imidazolium cross-link (DOGDIC) is energetically favourable. We have also conducted a comparison of these positions with those of the more abundant glucosepane cross-link, to determine any site preference. We show that when we consider both lysine and arginine AGEs, they exhibit a prevalence to form within the gap region of the collagen fibril.
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Keywords
Advanced glycation end products, Collagen, DOGDIC, Glucosepane, Glycation, Molecular dynamics, Protein cross-linking, Animals, Arginine, Binding Sites, Collagen Type I, Cross-Linking Reagents, Deoxyglucose, Glycation End Products, Advanced, Imidazoles, Lysine, Models, Molecular, Molecular Dynamics Simulation, Rats
Citation
Biophys Chem, 2016, 218 pp. 42 - 46