High-resolution structure of a new Tn antigen-binding lectin from Vatairea macrocarpa and a comparative analysis of Tn-binding legume lectins

Bruno Lopes Sousa; José Caetano Silva Filho; Prashant Kumar; Ronniery Ilário Pereira; Andrzej Łyskowski; Bruno Anderson Matias Rocha; Plínio Delatorre; Gustavo Arruda Bezerra; Celso Shiniti Nagano; Karl Gruber; Benildo Sousa Cavada

doi:10.1016/j.biocel.2014.12.002

High-resolution structure of a new Tn antigen-binding lectin from Vatairea macrocarpa and a comparative analysis of Tn-binding legume lectins

Int J Biochem Cell Biol. 2015 Feb:59:103-10. doi: 10.1016/j.biocel.2014.12.002. Epub 2014 Dec 12.

Affiliations

¹ Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Av. Mister Hull s/n, Bloco 907, Box 6043, 60440-970 Fortaleza, Ceará, Brazil.
² Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/3, A-8010 Graz, Austria.
³ Department of Biochemistry and Biotechnology, Rzeszów University of Technology, 35-959 Rzeszów, Poland.
⁴ Departamento de Biologia Molecular, Universidade Federal da Paraíba, Cidade Universitária, 58059-900 João Pessoa, Brazil.
⁵ Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.
⁶ Departamento de Engenharia de Pesca, Universidade Federal do Ceará, Av. Mister Hull s/n, Bloco 827, Fortaleza, Brazil.
⁷ Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Av. Mister Hull s/n, Bloco 907, Box 6043, 60440-970 Fortaleza, Ceará, Brazil. Electronic address: bscavada@ufc.br.

PMID: 25499445
DOI: 10.1016/j.biocel.2014.12.002

Abstract

Plant lectins have been studied as histological markers and promising antineoplastic molecules for a long time, and structural characterization of different lectins bound to specific cancer epitopes has been carried out successfully. The crystal structures of Vatairea macrocarpa (VML) seed lectin in complex with GalNAc-α-O-Ser (Tn antigen) and GalNAc have been determined at the resolution of 1.4Å and 1.7Å, respectively. Molecular docking analysis of this new structure and other Tn-binding legume lectins to O-mucin fragments differently decorated with this antigen provides a comparative binding profile among these proteins, stressing that subtle alterations that may not influence monosaccharide binding can, nonetheless, directly impact the ability of these lectins to recognize naturally occurring antigens. In addition to the specific biological effects of VML, the structural and binding similarities between it and other lectins commonly used as histological markers (e.g., VVLB4 and SBA) strongly suggest VML as a candidate tool for cancer research.

Keywords: Comparative analysis; Crystal structure; Dalbergieae tribe; Legume lectin; Tn antigen.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Acetylgalactosamine / chemistry
Antigens, Tumor-Associated, Carbohydrate / chemistry*
Antigens, Tumor-Associated, Carbohydrate / metabolism*
Binding Sites
Crystallography, X-Ray
Fabaceae / chemistry*
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Molecular Docking Simulation
Mucin-2 / chemistry
Plant Lectins / chemistry*
Plant Lectins / metabolism*
Structural Homology, Protein
Thermodynamics

Substances

Antigens, Tumor-Associated, Carbohydrate
Mucin-2
Plant Lectins
Tn antigen
Acetylgalactosamine