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Preferential sites for intramolecular glucosepane cross-link formation in type I collagen: A thermodynamic study

Collier, TA; Nash, A; Birch, HL; de Leeuw, NH; (2015) Preferential sites for intramolecular glucosepane cross-link formation in type I collagen: A thermodynamic study. Matrix Biology , 48 pp. 78-88. 10.1016/j.matbio.2015.06.001. Green open access

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Abstract

The extracellular matrix (ECM) undergoes progressive age-related stiffening and loss of proteolytic digestibility due to an increase in concentration of advanced glycation end products (AGEs). The most abundant AGE, glucosepane, accumulates in collagen with concentrations over 100 times greater than all other AGEs. Detrimental collagen stiffening properties are believed to play a significant role in several age-related diseases such as osteoporosis and cardiovascular disease. Currently little is known of the potential location of covalently cross-linked glucosepane formation within collagen molecules; neither are there reports on how the respective cross-link sites affect the physical and biochemical properties of collagen. Using fully atomistic molecular dynamics simulations (MD) we have identified six sites where the formation of a covalent intra-molecular glucosepane cross-link within a single collagen molecule in a fibrillar environment is energetically favourable. Identification of these favourable sites enables us to align collagen cross-linking with experimentally observed changes to the ECM. For example, formation of glucosepane was found to be energetically favourable within close proximity of the Matrix Metalloproteinase-1 (MMP1) binding site, which could potentially disrupt collagen degradation.

Type: Article
Title: Preferential sites for intramolecular glucosepane cross-link formation in type I collagen: A thermodynamic study
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.matbio.2015.06.001
Publisher version: http://dx.doi.org/10.1016/j.matbio.2015.06.001
Language: English
Additional information: © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Advanced glycation end products, Collagen, Glucosepane, Glycation, Molecular dynamics, Protein cross-linking
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1468967
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