Linked Life Data

12244479

Source:http://linkedlifedata.com/resource/pubmed/id/12244479

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-9-23
pubmed:abstractText
Binding to proteins usually induces perturbation of nuclear magnetic resonances of ligand molecules. Using sensitive nuclear magnetic resonance (NMR) spectroscopy techniques, these perturbations have been measured for heparin oligosaccharides in aqueous solution in the presence of proteins and the NMR data have been used to characterize the three-dimensional (3D) structure of the oligosaccharides in the bound state. The pentasaccharide corresponding to the active site of heparin/heparan sulfate for antithrombin (AT) adopts in the complex with the protein a conformation different from that in the absence of the protein. A notable difference involves the 2-O-sulfated iduronic acid (IdoA2S) residue, which is driven to adopt an exclusively skew-boat @affil2: 2S 0 form in the complex. In addition, complexing induces a change in the geometry around the glycosidic linkage between the nonreducing end glucosamine and the adjacent glucuronic acid residue as compared with the free state. NMR and molecular modeling data also indicate that the 2-O-sulfate group in the IdoA2S residue is not directly involved in binding to AT. This suggests that its role is mainly that of affecting the conformational equilibrium of this residue, leading to a 3D structure of pentasaccharide in the bound state that meets the stereochemical requirements of the receptor and results in high-affinity binding to the protein. On the other hand, NMR studies of heparin tetrasaccharides in the presence of fibroblast growth factors FGF-1 and FGF-2 indicate that FGF binding stabilizes the @affil1: 1C 4 conformation of the IdoA2S residue directly involved in binding. These studies also confirm the crucial role of the 6-O-sulfate group on at least one glucosamine residue in the formation of the complex with FGF-1 but not with FGF-2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0094-6176
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
325-34
pubmed:dateRevised
2006-3-7
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Active conformations of glycosaminoglycans. NMR determination of the conformation of heparin sequences complexed with antithrombin and fibroblast growth factors in solution.
pubmed:affiliation
Institute for Chemical and Biochemical Research G. Ronzoni, Milan, Italy.
pubmed:publicationType
Journal Article, Review