residues in the active site such as Asn385 and Asn379, which is consistent with the thermodynamic profile obtained with the ITC assays. There is a π-cation interaction between the electronegative dipole induced by the aromatic ring of Phe325 and the positive charge of the Man84 guanidine. As this guanidinium group is positively charged in solution, it is thus perfectly complementary to the electronegative pocket close to the calcium site and extending under Phe325 in L-SIGN (Fig. ). To note, the guanidinium group also contributes to the stabilization of two water molecules within the structure that contribute additional H-Bonds to the whole complex (Fig. ). These crystallographic water molecules, stabilized within the complex due to Man84, could participate to entropy contribution observed upon binding. Finally, comparison with the active site of DC-SIGN (PDB: 2IT6), revealed the atomic details that determine the selectivity of Man84 between the lectins (Fig. ). It lies in differences within the guanidium-binding pocket: all the side chains interacting with Man84 are exactly identical or equivalent in DC-SIGN and in L-SIGN except for N385, which is replaced by K373 in DC-SIGN.