Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine.

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.

SUBMITTER: Smith EW 

PROVIDER: S-EPMC4255719 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature