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- Title
Taxanes inhibit human TLR4 signaling by binding to MD-2
- Authors
Resman, Nuša; Gradišar, Helena; Vašl, Jožica; Keber, Mateja Manček; Pristovšek, Primož; Jerala, Roman
- Abstract
Abstract: LPS is the primary ligand of Toll-like receptor 4, activating it through binding to its accessory protein MD-2. Murine but not human cells expressing MD-2/TLR4 are also activated by paclitaxel. Paclitaxel binds to human MD-2. The binding site of paclitaxel overlaps with the binding site of bis-ANS and LPS, which results in the ability of taxanes to inhibit LPS signaling in the system with human receptors. Circular dichroic spectra of human MD-2 indicated differences in the chemical environment in the presence of paclitaxel and docetaxel. Molecular docking identified the interacting residues of MD-2 and suggests that hydrophobic interactions govern the binding, while the C-3′N group where the paclitaxel and docetaxel differ is exposed on the surface of MD-2.
- Subjects
DITERPENES; TAXUS; LIGAND binding (Biochemistry); PROTEIN binding; PACLITAXEL; DOCETAXEL; POLYSACCHARIDES
- Publication
FEBS Letters, 2008, Vol 582, Issue 28, p3929
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2008.10.037