Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine

[Image: see text] 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...

Descripción completa

Detalles Bibliográficos
Autores principales: Smith, Emmanuel W., Liu, Yan, Getschman, Anthony E., Peterson, Francis C., Ziarek, Joshua J., Li, Rongshi, Volkman, Brian F., Chen, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255719/
https://www.ncbi.nlm.nih.gov/pubmed/25356720
http://dx.doi.org/10.1021/jm501194p
Descripción
Sumario:[Image: see text] 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.

Ejemplares similares