Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine. J Med Chem 2014 Nov 26;57(22):9693-9
Date
10/31/2014Pubmed ID
25356720Pubmed Central ID
PMC4255719DOI
10.1021/jm501194pScopus ID
2-s2.0-84913593689 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
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.
Author List
Smith EW, Liu Y, Getschman AE, Peterson FC, Ziarek JJ, Li R, Volkman BF, Chen YAuthors
Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of WisconsinBrian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsBinding Sites
Chemokine CXCL12
Chemotaxis
Crystallography, X-Ray
Drug Design
Humans
Ligands
Magnetic Resonance Spectroscopy
Molecular Docking Simulation
Protein Binding
Protein Structure, Tertiary
Receptors, CXCR4
Signal Transduction
Structure-Activity Relationship