Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-6-22
pubmed:abstractText
The linear, sulfated polysaccharide heparan sulfate occupies a pivotal position in intercellular signalling events, interacting with numerous proteins on the cell surface and in the extracellular matrix. Its complex sequences suggest high potential information content but, despite extensive efforts, a clear relationship between its substitution pattern and biological activity remains elusive. This results from technical limitations, compounded by attempts to correlate substitution pattern directly with activity without considering other conformational factors. For a series of systematically modified analogues of heparan sulfate, the relationship between substitution pattern and experimental (13)C NMR chemical shifts, which act as reporters of the presence of conformational change, particularly around the glycosidic linkages, was explored through chemometric analysis. From analysis of the experimental data it was evident that wide linkage variation arose from O-sulfation in iduronate and N-sulfation in glucosamine residues but, their effects were distinct, while 6-O-sulfation had much less impact. Models of saccharide sequences showed that the maximum spread of variation in glycosidic linkages occurred before maximum sequence diversity and revealed a highly degenerate system: a fraction of possible sequences is sufficient to provide diverse backbone conformations to satisfy particular protein binding requirements. The unique information content potentially available in HS sequences, defined ultimately by conformation, is vastly inferior to the potential sequence diversity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1742-2051
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
902-8
pubmed:dateRevised
2011-5-16
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Conformational degeneracy restricts the effective information content of heparan sulfate.
pubmed:affiliation
School of Biological Sciences, University of Liverpool, Liverpool, UK L69 7ZB.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't