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...

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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
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author Smith, Emmanuel W.
Liu, Yan
Getschman, Anthony E.
Peterson, Francis C.
Ziarek, Joshua J.
Li, Rongshi
Volkman, Brian F.
Chen, Yu
author_facet Smith, Emmanuel W.
Liu, Yan
Getschman, Anthony E.
Peterson, Francis C.
Ziarek, Joshua J.
Li, Rongshi
Volkman, Brian F.
Chen, Yu
author_sort Smith, Emmanuel W.
collection PubMed
description [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.
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spelling pubmed-42557192015-10-30 Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine Smith, Emmanuel W. Liu, Yan Getschman, Anthony E. Peterson, Francis C. Ziarek, Joshua J. Li, Rongshi Volkman, Brian F. Chen, Yu J Med Chem [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. American Chemical Society 2014-10-30 2014-11-26 /pmc/articles/PMC4255719/ /pubmed/25356720 http://dx.doi.org/10.1021/jm501194p Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Smith, Emmanuel W.
Liu, Yan
Getschman, Anthony E.
Peterson, Francis C.
Ziarek, Joshua J.
Li, Rongshi
Volkman, Brian F.
Chen, Yu
Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine
title Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine
title_full Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine
title_fullStr Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine
title_full_unstemmed Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine
title_short Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine
title_sort structural analysis of a novel small molecule ligand bound to the cxcl12 chemokine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255719/
https://www.ncbi.nlm.nih.gov/pubmed/25356720
http://dx.doi.org/10.1021/jm501194p
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