Identification of an antithrombotic allosteric modulator that acts through helix 8 of PAR1

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 7; pp. 2951 - 2956
• Main Authors: Dowal, Louisa, Sim, Derek S, Dilks, James R, Blair, Price, Beaudry, Sarah, Denker, Bradley M, Koukos, Georgios, Kuliopulos, Athan, Flaumenhaft, Robert
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.02.2011; National Acad Sciences
• Subjects: Aggregation; Agonists; Allosteric Regulation - physiology; Amino acids; Animals; Antithrombins - metabolism; Binding sites; Biological Sciences; Blood platelets; Calcium - metabolism; Cell Line; Dogs; Epinephrine; Flow Cytometry; Luciferases; Modulated signal processing; Molecules; P-Selectin - metabolism; Peptide Fragments - metabolism; Platelet activation; Platelet Aggregation; Platelets; Protein Structure, Secondary - physiology; Proteins; Receptor, PAR-1 - agonists; Receptor, PAR-1 - metabolism; Receptors; Receptors, G-Protein-Coupled - metabolism; Secretion; Signal transduction; Signal Transduction - physiology; Thrombosis; Thrombosis - metabolism

G protein-coupled receptors (GPCRs) can assume multiple conformations and possess multiple binding sites. Whereas endogenous agonists acting at the orthosteric binding site stabilize the active receptor conformation, small molecules that act at nonorthosteric sites can stabilize alternative conforma...