6VC4

Peanut lectin complexed with S-beta-D-Thiogalactopyranosyl beta-D-glucopyranoside derivative (STGD)

Summary for 6VC4

• Entry DOI: 10.2210/pdb6vc4/pdb
• Descriptor: Galactose-binding lectin, (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-{[(2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-({[(1-{[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-methoxytetrahydro-2H-pyran-2-yl]methyl}-1H-1,2,3-triazol-4-yl)methyl]sulfanyl}methyl)tetrahydro-2H-pyran-2-yl]sulfanyl}tetrahydro-2H-pyran-3,4,5-triol (non-preferred name), MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: beta-galactosylamides, beta-thiogalactosides, peanut agglutinin, glycomimetics, sugar binding protein
• Biological source: Arachis hypogaea (Peanut)
• Total number of polymer chains: 4
• Total formula weight: 103742.57

Authors

Otero, L.H.,Primo, E.D.,Cagnoni, A.J.,Cano, M.E.,Klinke, S.,Goldbaum, F.A.,Uhrig, M.L. (deposition date: 2019-12-20, release date: 2020-10-28, Last modification date: 2023-10-11)

Primary citation

Cagnoni, A.J.,Primo, E.D.,Klinke, S.,Cano, M.E.,Giordano, W.,Marino, K.V.,Kovensky, J.,Goldbaum, F.A.,Uhrig, M.L.,Otero, L.H.
Crystal structures of peanut lectin in the presence of synthetic beta-N- and beta-S-galactosides disclose evidence for the recognition of different glycomimetic ligands.
Acta Crystallogr D Struct Biol, 76:1080-1091, 2020

PubMed 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.

PubMed: 33135679
DOI: 10.1107/S2059798320012371

Experimental method

X-RAY DIFFRACTION (1.9 Å)