Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine.
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ABSTRACT:
SUBMITTER: Smith EW
PROVIDER: S-EPMC4255719 | biostudies-literature | 2014 Nov
REPOSITORIES: biostudies-literature
Publications
Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine.
Smith Emmanuel W EW Liu Yan Y Getschman Anthony E AE Peterson Francis C FC Ziarek Joshua J JJ Li Rongshi R Volkman Brian F BF Chen Yu Y
Journal of medicinal chemistry 20141113 22
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. ...[more]
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