Abstract
CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Å resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of CXCR4. The complex structure reveals binding hot spots for future inhibitor design and suggests a new approach to targeting CXCL12-CXCR4 signaling in drug discovery.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Antineoplastic Agents / chemistry*
-
Binding Sites
-
Chemokine CXCL12 / chemistry*
-
Chemotaxis
-
Crystallography, X-Ray / methods*
-
Drug Design
-
Humans
-
Ligands
-
Magnetic Resonance Spectroscopy
-
Molecular Docking Simulation
-
Protein Binding
-
Protein Structure, Tertiary
-
Receptors, CXCR4 / chemistry*
-
Signal Transduction
-
Structure-Activity Relationship
Substances
-
Antineoplastic Agents
-
CXCL12 protein, human
-
CXCR4 protein, human
-
Chemokine CXCL12
-
Ligands
-
Receptors, CXCR4