Partially Glycosylated Dendrimers Block MD-2 and Prevent TLR4-MD-2-LPS Complex Mediated Cytokine Responses
Figure 5
Crystal structure of human MD-2 with PDB entry 2E56 displayed as its electrostatic potential surface.
(A – left hand side figure):- Residues Arg90, Lys91, Ser118 and Lys122 on human MD-2 form electrostatic interactions with lipid A. The interaction of Lys122 and Arg90 with the hydrophilic moiety of lipid A tethers LPS to human MD-2's cavity [15]. The 4′ phosphate on lipid A's first glucosamine binds to Ser118 and the 1′ phosphate on lipid A's second glucosamine binds to Lys122. In addition, Tyr102 is crucial for the subsequent hydrogen bond interaction of the human MD-2-LPS complex with human TLR4 [55]. (B – middle figure):- The residues Lys91, Arg96, Tyr102 and Ser118 form electrostatic interactions with the partially glycosylated dendrimer. (C – right hand side figure):- Human MD-2 is shown in its “top right” orientation. The residues Ser98, Tyr102, Arg106, Lys109, Thr112, Asn114 and Thr116 form electrostatic interactions with the partially glycosylated dendrimer. These residues, which border the entrance of human MD-2's hydrophobic pocket, are labelled in the figures.