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

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dc.citation.volume48
dc.contributor.authorCollier TA
dc.contributor.authorNash A
dc.contributor.authorBirch HL
dc.contributor.authorde Leeuw NH
dc.date.available2015-06-01
dc.date.issued2015-06-01
dc.description.abstractThe 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.
dc.description.confidentialfalse
dc.format.extent78 - 88
dc.identifier.citationMatrix Biology, 2015, 48 pp. 78 - 88
dc.identifier.doi10.1016/j.matbio.2015.06.001
dc.identifier.elements-id284087
dc.identifier.harvestedMassey_Dark
dc.identifier.issn1569-1802
dc.publisherElsevier
dc.relation.isPartOfMatrix Biology
dc.relation.urihttps://www.sciencedirect.com/science/article/pii/S0945053X15001195?via=ihub
dc.rightsOpen Access funded by Biotechnology and Biological Sciences Research Council under a Creative Commons license
dc.subjectCollagen
dc.subjectGlycation
dc.subjectMolecular dynamics
dc.subjectProtein cross-linking
dc.subjectGlucosepane
dc.subjectAdvanced glycation end products
dc.subject.anzsrc06 Biological Sciences
dc.titlePreferential sites for intramolecular glucosepane cross-link formation in type I collagen: A thermodynamic study
dc.typeJournal article
pubs.notesNot known
pubs.organisational-group/Massey University
pubs.organisational-group/Massey University/College of Sciences
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