Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine
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- 作者：Emmanuel W. Smith ; Yan Liu ; Anthony E. Getschman ; Francis C. Peterson ; Joshua J. Ziarek ; Rongshi Li ; Brian F. Volkman ; Yu Chen
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：November 26, 2014
- 年：2014
- 卷：57
- 期：22
- 页码：9693-9699
- 全文大小：319K
- ISSN：1520-4804
文摘
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 脜 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鈥揅XCR4 signaling in drug discovery.