title: Combining 3D structure with glycan array data provides insight into the origin of glycan specificity.
abstract: Defining how a glycan-binding protein (GBP) specifically selects its cognate glycan from among the ensemble of glycans within the cellular glycome is an area of intense study. Powerful insight into recognition mechanisms can be gained from 3D structures of GBPs complexed to glycans; however, such structures remain difficult to obtain experimentally. Here an automated 3D structure generation technique, called computational carbohydrate grafting, is combined with the wealth of specificity information available from glycan array screening. Integration of the array data with modeling and crystallography allows generation of putative co-complex structures that can be objectively assessed and iteratively altered until a high level of agreement with experiment is achieved. Given an accurate model of the co-complexes, grafting is also able to discern which binding determinants are active when multiple potential determinants are present within a glycan. In some cases, induced fit in the protein or glycan was necessary to explain the observed specificity, while in other examples a revised definition of the minimal binding determinants was required. When applied to a collection of 10 GBP-glycan complexes, for which crystallographic and array data have been reported, grafting provided a structural rationalization for the binding specificity of >90% of 1223 arrayed glycans. A webtool that enables researchers to perform computational carbohydrate grafting is available at www.glycam.org/gr (accessed 03 March 2016).
authors.affiliation: Complex Carbohydrate Research Center and Department of Biochemistry, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Grant
authors.affiliation: Complex Carbohydrate Research Center and Department of Biochemistry, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Tessier
authors.affiliation: New York University Department of Chemistry, Biomedical Chemistry Institute, 100 Washington Square East, Room 1001, New York, NY 10003, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Meche
authors.affiliation: New York University Department of Chemistry, Biomedical Chemistry Institute, 100 Washington Square East, Room 1001, New York, NY 10003, USA.
authors.forename: Lara K
authors.initials: LK
authors.lastname: Mahal
authors.affiliation: New York University Department of Chemistry, Biomedical Chemistry Institute, 100 Washington Square East, Room 1001, New York, NY 10003, USA.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Foley
authors.affiliation: Complex Carbohydrate Research Center and Department of Biochemistry, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
mesh_terms: D002241:Carbohydrates / Q000737:chemistry; D002352:Carrier Proteins; D019295:Computational Biology; D008968:Molecular Conformation; D011134:Polysaccharides / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002241:Carbohydrates; D002352:Carrier Proteins; D011134:Polysaccharides; D011506:Proteins
keywords: 3D structure; binding determinant; glycan array screening; glycan-binding protein; lectin specificity