title: Crystallographic and in silico analysis of the sialoside-binding characteristics of the Siglec sialoadhesin.
abstract: The Siglec family of receptors mediates cell-surface interactions through recognition of sialylated glycoconjugates. Previously reported structures of the N-terminal domain of the Siglec sialoadhesin (SnD1) in complex with various sialic acid analogs revealed the structural template for sialic acid binding. To characterize further the carbohydrate-binding properties, we have determined the crystal structures of SnD1 in the absence of ligand, and in complex with 2-benzyl-Neu5NPro and 2-benzyl-Neu5NAc. These structures reveal that SnD1 undergoes very few structural changes on ligand binding and detail how two novel classes of sialic acid analogs bind, one of which unexpectedly can induce Siglec dimerization. In conjunction with in silico analysis, this set of structures informs us about the design of putative ligands with enhanced binding affinities and specificities to different Siglecs, and provides data with which to test the effectiveness of different computational drug design protocols.
authors.affiliation: CR-UK Receptor Structure Research Group, Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Headington, Oxford OX3 7BN, UK. nathan.zaccai@bristol.ac.uk
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Zaccai
authors.forename: Andrew P
authors.initials: AP
authors.lastname: May
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robinson
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Burtnick
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
authors.forename: Reinhard
authors.initials: R
authors.lastname: Brossmer
authors.forename: Soerge
authors.initials: S
authors.lastname: Kelm
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
mesh_terms: D000465:Algorithms; D000818:Animals; D016466:CHO Cells; D019295:Computational Biology; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*
chemical_list: C517516:2-benzyl-5-N-acetylneuraminic acid; C517517:2-benzyl-5-N-propanoylneuraminic acid; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D063267:Sialic Acid Binding Ig-like Lectin 1; D012794:Sialic Acids