title: The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin interaction.
abstract: Vascular cell adhesion molecule 1 (VCAM-1) represents a structurally and functionally distinct class of immunoglobulin superfamily molecules that bind leukocyte integrins and are involved in inflammatory and immune functions. X-ray crystallography defines the three-dimensional structure of the N-terminal two-domain fragment that participates in ligand binding. Residues in domain 1 important for ligand binding reside in the C-D loop, which projects markedly from one face of the molecule near the contact between domains 1 and 2. A cyclic peptide that mimics this loop inhibits binding of alpha 4 beta 1 integrin-bearing cells to VCAM-1. These data demonstrate how crystallographic structural information can be used to design a small molecule inhibitor of biological function.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
authors.forename: R B
authors.initials: RB
authors.lastname: Pepinsky
authors.forename: T
authors.initials: T
authors.lastname: Stehle
authors.forename: J H
authors.initials: JH
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Karpusas
authors.forename: B
authors.initials: B
authors.lastname: Browning
authors.forename: L
authors.initials: L
authors.lastname: Osborn
mesh_terms: D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D010456:Peptides, Cyclic; D019010:Vascular Cell Adhesion Molecule-1