title: Glycosaminoglycan-protein interactions: definition of consensus sites in glycosaminoglycan binding proteins.
abstract: Although interactions of proteins with glycosaminoglycans (GAGs), such as heparin and heparan sulphate, are of great biological importance, structural requirements for protein-GAG binding have not been well-characterised. Ionic interactions are important in promoting protein-GAG binding. Polyelectrolyte theory suggests that much of the free energy of binding comes from entropically favourable release of cations from GAG chains. Despite their identical charges, arginine residues bind more tightly to GAGs than lysine residues. The spacing of these residues may determine protein-GAG affinity and specificity. Consensus sequences such as XBBBXXBX, XBBXBX and a critical 20 A spacing of basic residues are found in some protein sites that bind GAG. A new consensus sequence TXXBXXTBXXXTBB is described, where turns bring basic interacting amino acid residues into proximity. Clearly, protein-GAG interactions play a prominent role in cell-cell interaction and cell growth. Pathogens including virus particles might target GAG-binding sites in envelope proteins leading to infection.
authors.affiliation: Division of Medicinal and Natural Products Chemistry, University of Iowa, Iowa City 52242, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Hileman
authors.forename: J R
authors.initials: JR
authors.lastname: Fromm
authors.forename: J M
authors.initials: JM
authors.lastname: Weiler
authors.forename: R J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D001665:Binding Sites; D002240:Carbohydrate Sequence; D016384:Consensus Sequence / Q000235:genetics; D006025:Glycosaminoglycans / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D006025:Glycosaminoglycans; D011506:Proteins