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Taxanes inhibit human TLR4 signaling by binding to MD‐2
Author(s) -
Resman Nuša,
Gradišar Helena,
Vašl Jožica,
Keber Mateja Manček,
Pristovšek Primož,
Jerala Roman
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.10.037
Subject(s) - chemistry , signal transduction , microbiology and biotechnology , biochemistry , biology
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.