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Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine. J Med Chem 2014 Nov 26;57(22):9693-9

Date

10/31/2014

Pubmed ID

25356720

Pubmed Central ID

PMC4255719

DOI

10.1021/jm501194p

Scopus ID

2-s2.0-84913593689   16 Citations

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.

Author List

Smith EW, Liu Y, Getschman AE, Peterson FC, Ziarek JJ, Li R, Volkman BF, Chen Y

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian 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 Agents
Binding 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
jenkins-FCD Prod-444 eb4ebd1a08581aba961d3befd3b851a3c3ec6b46