Analysis of Photo-crosslinking Sites of Antagonists and Agonists in CCR5 and CXCR4
EMSL Project ID
35592
Abstract
The primary objective of our proposed studies are to characterize the residues on CCR5 and CXCR4 (likely to be deep within biological membranes) that directly mediate the interactions with agonist and antagonist compounds, employing FT-ICR and LC-ESI-Orbitrap mass spectrometry. We would like to collaborate with EMSL staff on analyzing and publishing the cross-linking data.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, and at present approximately 50% of drugs in use or under development 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 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
Large-Scale EMSL Research
Start Date
2009-10-08
End Date
2011-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members