Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-α) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and L-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties.
BC2L-C N-terminal lectin domain complexed with histo blood group oligosaccharides provides new structural information / R. Bermeo, A. Bernardi, A. Varrot. - In: MOLECULES. - ISSN 1420-3049. - 25:2(2020 Jan), pp. 248.1-248.15.
|Titolo:||BC2L-C N-terminal lectin domain complexed with histo blood group oligosaccharides provides new structural information|
BERMEO MALO, RAFAEL (Primo)
BERNARDI, ANNA (Secondo)
|Parole Chiave:||Blood group antigen; Crystallography; Fucosides; TNF-like lectin|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||gen-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/molecules25020248|
|Appare nelle tipologie:||01 - Articolo su periodico|