PDBsum entry 6vc3

Sugar binding protein

PDB id: 6vc3

Contents

Protein chains

232 a.a.

Ligands

QWJ ×3

Metals

_CA ×4

_MN ×4

Waters ×554

References listed in PDB file

Key reference

• Title: Crystal structures of peanut lectin in the presence of synthetic β-N- And β-S-Galactosides disclose evidence for the recognition of different glycomimetic ligands.
• Authors: A.J.Cagnoni, E.D.Primo, S.Klinke, M.E.Cano, W.Giordano, K.V.Mariño, J.Kovensky, F.A.Goldbaum, M.L.Uhrig, L.H.Otero.
• Ref.: Acta Crystallogr D Struct Biol, 2020, 76, 1080-1091. [DOI no: 10.1107/S2059798320012371]
• PubMed id: 33135679

Abstract

Carbohydrate-lectin interactions are involved in important cellular recognition processes, including viral and bacterial infections, inflammation and tumor metastasis. Hence, structural studies of lectin-synthetic glycan complexes are essential for understanding lectin-recognition processes and for the further design of promising chemotherapeutics that interfere with sugar-lectin interactions. Plant lectins are excellent models for the study of the molecular-recognition process. Among them, peanut lectin (PNA) is highly relevant in the field of glycobiology because of its specificity for β-galactosides, showing high affinity towards the Thomsen-Friedenreich antigen, a well known tumor-associated carbohydrate antigen. Given this specificity, PNA is one of the most frequently used molecular probes for the recognition of tumor cell-surface O-glycans. Thus, it has been extensively used in glycobiology for inhibition studies with a variety of β-galactoside and β-lactoside ligands. Here, crystal structures of PNA are reported in complex with six novel synthetic hydrolytically stable β-N- and β-S-galactosides. These complexes disclosed key molecular-binding interactions of the different sugars with PNA at the atomic level, revealing the roles of specific water molecules in protein-ligand recognition. Furthermore, binding-affinity studies by isothermal titration calorimetry showed dissociation-constant values in the micromolar range, as well as a positive multivalency effect in terms of affinity in the case of the divalent compounds. Taken together, this work provides a qualitative structural rationale for the upcoming synthesis of optimized glycoclusters designed for the study of lectin-mediated biological processes. The understanding of the recognition of β-N- and β-S-galactosides by PNA represents a benchmark in protein-carbohydrate interactions since they are novel synthetic ligands that do not belong to the family of O-linked glycosides.