Milanos L, Saleh N, Kling R, Kaindl J, Tschammer N, Clark T (2016)
Publication Status: Published
Publication Type: Journal article
Publication year: 2016
Publisher: WILEY-V C H VERLAG GMBH
Book Volume: 55
Pages Range: 15277-15281
Journal Issue: 49
The chemokine receptor CXCR3 is a G protein-coupled receptor that conveys extracellular signals into cells by changing its conformation upon ligand binding. We previously hypothesized that small-molecule allosteric CXCR3-agonists do not bind to the same allosteric binding pocket as 8-azaquinazolinone-based negative allosteric modulators. We have now performed molecular-dynamics (MD) simulations with metadynamics enhanced sampling on the CXCR3 system to refine structures and binding modes and to predict the CXCR3-binding affinities of the biased allosteric agonist FAUC1036 and the negative allosteric modulator RAMX3. We have identified two distinct binding sites; a shallow and a second deeper pocket to which the biased allosteric agonist FAUC1036 and negative allosteric modulator RAMX3 bind, respectively.
APA:
Milanos, L., Saleh, N., Kling, R., Kaindl, J., Tschammer, N., & Clark, T. (2016). Identification of Two Distinct Sites for Antagonist and Biased Agonist Binding to the Human Chemokine Receptor CXCR3. Angewandte Chemie International Edition, 55(49), 15277-15281. https://dx.doi.org/10.1002/anie.201607831
MLA:
Milanos, Lampros, et al. "Identification of Two Distinct Sites for Antagonist and Biased Agonist Binding to the Human Chemokine Receptor CXCR3." Angewandte Chemie International Edition 55.49 (2016): 15277-15281.
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