Structural characterization of a Vatairea macrocarpa lectin in complex with a tumor-associated antigen: A new tool for cancer research

Bruno L Sousa; José C Silva-Filho; Prashant Kumar; Melissa A Graewert; Ronniery I Pereira; Rodrigo M S Cunha; Kyria S Nascimento; Gustavo A Bezerra; Plínio Delatorre; Kristina Djinovic-Carugo; Celso S Nagano; Karl Gruber; Benildo S Cavada

doi:10.1016/j.biocel.2015.12.016

Structural characterization of a Vatairea macrocarpa lectin in complex with a tumor-associated antigen: A new tool for cancer research

Int J Biochem Cell Biol. 2016 Mar:72:27-39. doi: 10.1016/j.biocel.2015.12.016. Epub 2016 Jan 2.

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 European Molecular Biology Laboratory, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany.
⁴ Centro de Ciências Agrárias e Biológicas, Universidade do Vale do Acaraú, Rua Gerardo Rangel s/n, 62041-040, Sobral, Brazil.
⁵ Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), Vienna Biocenter Campus 5, 1030 Vienna, Austria.
⁶ Departamento de Biologia Molecular, Universidade Federal da Paraíba, Cidade Universitária, 58059-900, João Pessoa, Brazil.
⁷ Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), Vienna Biocenter Campus 5, 1030 Vienna, Austria; Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.
⁸ Departamento de Engenharia de Pesca, Universidade Federal do Ceará, Av. Mister Hull s/n, Bloco 827, Fortaleza, Brazil.

PMID: 26751394
DOI: 10.1016/j.biocel.2015.12.016

Abstract

Legume lectins are the most thoroughly studied group of lectins and have been widely linked to many pathological processes. Their use as immunohistochemistry markers for cell profiling and cancer diagnosis have made these molecules important tools for immunological studies and have stimulated the prospection and characterization of new lectins. The crystal structures of a recombinant seed lectin from Vatairea macrocarpa (rVML) and its complexes with GalNAcα1-O-Ser, GalNAc and α-lactose, have been determined at 1.90, 1.97, 2.70 and 1.83Å resolution, respectively. Small angle X-ray scattering and calorimetry assays have confirmed the same pH stable oligomerization pattern and binding profiles proposed for its wild-type counterpart. In silico analyzes have explored the potential of this recombinant lectin as new tool for cancer research through a comparative profile with other legume lectins widely used for cancer diagnosis and prognosis. The results suggest the recognition of specific epitopes exhibited on different cancer cells as a process that relies on the disposition of hydrophobic clusters and charged regions around the lectin carbohydrate-binding site, favouring the anchorage of different groups in the antigen boundaries, highlighting the different potential of each analyzed lectin. In conclusion, the experimental results and comparative analysis show that rVML is as a promising tool for cancer research, able to bind with high affinity specific tumor-associated antigens, highly stable and easily produced.

Keywords: Cancer research; Crystal structure; Histochemistry; Legume lectin; Tn antigen; Vatairea macrocarpa.

Publication types

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

MeSH terms

Acetylgalactosamine / metabolism
Antigens, Tumor-Associated, Carbohydrate / metabolism*
Fabaceae / chemistry*
Lactose / metabolism
Molecular Docking Simulation
Neoplasms / metabolism*
Plant Lectins / chemistry*
Plant Lectins / metabolism*
Protein Binding
Protein Conformation

Substances

Antigens, Tumor-Associated, Carbohydrate
Plant Lectins
Tn antigen
Lactose
Acetylgalactosamine