title: Intra-molecular lysine-arginine derived advanced glycation end-product cross-linking in Type I collagen: A molecular dynamics simulation study.
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.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Collier
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Nash
authors.affiliation: Institute of Orthopaedics and Musculoskeletal Science, UCL, RNOH Stanmore Campus, London, United Kingdom.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Birch
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom; School of Chemistry, Cardiff University, Cardiff CF10 1DF, United Kingdom. Electronic address: DeLeeuwN@cardiff.ac.uk.
authors.forename: Nora H
authors.initials: NH
authors.lastname: de Leeuw
mesh_terms: D000818:Animals; D001120:Arginine; D001665:Binding Sites; D024042:Collagen Type I / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003847:Deoxyglucose / Q000031:analogs & derivatives; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry; D008239:Lysine; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D051381:Rats
chemical_list: D024042:Collagen Type I; D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; D007093:Imidazoles; C543060:glucosepane; C029899:imidazole; D001120:Arginine; D003847:Deoxyglucose; C016350:3-deoxyglucosone; D008239:Lysine
keywords: Advanced glycation end products; Collagen; DOGDIC; Glucosepane; Glycation; Molecular dynamics; Protein cross-linking