Versatile PGRPLC-mediated modulation of Anopheles gambiae antibacterial defense and infection with malaria parasites

AgPGRPLC-TCT complexes In the AgPGRPLC1-TCT model, the ligand conformation remained unchanged. In AgPGRPLC2-TCT small rotations of torsion angles between L-Ala and D-Glu were necessary to relieve steric clashes between the carboxyl group of D-Glu and P92. In AgPGRPLC1 and LC3 however, Pro92 is replaced by a Lys, which permits placement without a bump. Most conserved interactions are maintained in AgPGRPLC2-TCT interactions are maintained while the repositioned carboxyl group of D-Glu approaches D147 (which is equivalent to K147 and A148 in AgPGRPLC1 and LC3, respectively) at H-bonding distance. In the AgPGRPLC3-TCT complex, a small rotation around the glycosidicGlcNAc/MurNAc (anhydro) bond elevates the pyranose ring of GlcNAc by almost 0.7 Å away from the glycan-binding cleft. This motion was a result of non-permissive van der Waals contacts with the phenyl group of F150. This unique Phe replaces a conserved Thr residue (T149 in AgPGRPLC1 and LC2) whose Oγ atom forms a water-mediated H-bond with ring-O5 atom of GlcNAc. However, the lost H-bond is replaced by π-stacking between F150 and the ring of GlcNAc (Table S4), a favorable interaction in proteinsugar complexes. Compared to the DmPGRP-LCx-TCT complex, three hydrogen bonds are lost in AgPGRPLC1-TCT and AgPGRPLC2-TCT; for AgPGRPLC1 due to replacement of residues W, H and S with T, A and K at positions 61, 143 and 147, respectively and for AgPGRPLC2 due to replacement of residues H, K with residues S, P at positions 143 and 92, respectively and torsional shifts in TCT. Two such bonds are lost in the AgPGRPLC3-TCT complex (residue F150 and A148 in place of T and S in LCx). One additional H-bond is gained in PGRPLC1-TCT and PGRPLC2-TCT, whereby atoms OH of Y56 and N of G93 interact with O6 of MurNAc(anhydro) and O of D-Ala, respectively. The AgPGRPLC3-TCT interaction is considerably more hydrophobic than the one observed in AgPGRPLC1-TCT and AgPGRPLC2TCT (Table S4).