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

Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5714-8. doi: 10.1073/pnas.92.12.5714.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / metabolism
  • Computer Graphics
  • Crystallography, X-Ray
  • Integrin alpha4beta1
  • Integrins / antagonists & inhibitors*
  • Integrins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Vascular Cell Adhesion Molecule-1

Substances

  • Cell Adhesion Molecules
  • Integrin alpha4beta1
  • Integrins
  • Peptides, Cyclic
  • Vascular Cell Adhesion Molecule-1