Determination of the CCR5 and CXCR4 Antagonist and Agonist Binding Site.
EMSL Project ID
25662a
Abstract
This proposal focuses on determining the locations of the agonist and antagonist binding pockets for the 7-transmembrane spanning G-Protein coupled receptors (GPCR) CCR5 and CXCR4. G-protein coupled receptors play a central role in signal transduction in all domains of life, at present approximately 50% of drugs in use target GPCRs. CCR5 and CXCR4 have been identified as the major entry cofactors for most primary or clinical isolates of HIV from patients. Agonists and antagonists to CCR5 and CXCR4 have been demonstrated to inhibit HIV infection leading to the development of many antiviral compounds by the pharmaceutical industry that are in preclinical and clinical trials. The primary objective of our studies is to characterize the residues on CCR5 and CXCR4 that directly mediate the interactions with agonist and antagonist compounds employing FT-ICR and LC-ESI-TOF mass spectrometry. The anticipated impact of our studies will be the generation of information facilitating the design of improved agents to block HIV infection and more generally increase understanding of the potentially conserved mechanisms of ligand binding shared by family A members of the G protein coupled receptor super-family.
Project Details
Project type
Limited Scope
Start Date
2008-09-30
End Date
2008-11-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members