Structural Analysis of Chemokine Receptor–Ligand Interactions

This
review focuses on the construction and application of structural chemokine
receptor models for the elucidation of molecular determinants of chemokine
receptor modulation and the structure-based discovery and design of
chemokine receptor ligands. A comparative analysis of ligand binding
pockets in chemokine receptors is presented, including a detailed
description of the CXCR4, CCR2, CCR5, CCR9, and US28 X-ray structures,
and their implication for modeling molecular interactions of chemokine
receptors with small-molecule ligands, peptide ligands, and large
antibodies and chemokines. These studies demonstrate how the integration
of new structural information on chemokine receptors with extensive
structure–activity relationship and site-directed mutagenesis
data facilitates the prediction of the structure of chemokine receptor–ligand
complexes that have not been crystallized. Finally, a review of structure-based
ligand discovery and design studies based on chemokine receptor crystal
structures and homology models illustrates the possibilities and challenges
to find novel ligands for chemokine receptors.