BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 Jan 16

PMID 31936166

Citations 6

Authors

Rafael Bermeo

Anna Bernardi

Annabelle Varrot

Affiliations

Soon will be listed here.

Abstract

Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen , 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-) 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.

Citing Articles

Tandem-repeat lectins: structural and functional insights.

Olvera-Lucio F, Riveros-Rosas H, Quintero-Martinez A, Hernandez-Santoyo A Glycobiology. 2024; 34(7).

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Glycomimetic antagonists of BC2L-C lectin: insights from molecular dynamics simulations.

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Identification of New L-Fucosyl and L-Galactosyl Amides as Glycomimetic Ligands of TNF Lectin Domain of BC2L-C from .

Mazzotta S, Antonini G, Vasile F, Gillon E, Lundstrom J, Varrot A Molecules. 2023; 28(3).

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Targeting a Multidrug-Resistant Pathogen: First Generation Antagonists of 's BC2L-C Lectin.

Bermeo R, Lal K, Ruggeri D, Lanaro D, Mazzotta S, Vasile F ACS Chem Biol. 2022; 17(10):2899-2910.

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