O-methylation of sugars is an uncommon modification with not fully understood function. Recently, it was described as a pathogen-associated molecular pattern (PAMP), since its interaction with the immune system effector lectin Lb-Tec2 was described [1]. Lectins are proteins able to reversibly bind glycoconjugates with high specificity. Besides their important role in the innate immune system, they play a crucial role in many other biological processes, including both mutualistic and parasitic interactions between microorganisms and hosts [2]. Lectin/saccharide interaction is mostly mediated via hydrogen bonds. However, the importance of non-polar interactions, such as CH-π interactions between aromatic amino acids and apolar part of carbohydrate molecules, was shown recently [3].
Our research is focused on studying lectins from entomopathogenic bacterium Photorhabdus laumondii, which is known for its complicated life-cycle, including mutualism and pathogenicity towards two different invertebrate hosts. The contribution is focused on the PLL2 lectin, which forms a 7-bladed β-propeller with two sets of binding sites situated in between the blades. PLL2 has been confirmed to bind multiple monosaccharides, including d-glucose and 3-O-methyl-d-glucose. SPR measurement revealed two orders of magnitude stronger inhibition potential of 3-O-methyl-d-glucose compared to d-glucose. X-ray structures showed both ligands are able to occupy one set of sites (“polar” sites), but only 3-O-methyl-d-glucose was found in the second set of sites (“hydrophobic” sites).