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Article

Directed Mutagenesis for Arginine Substitution of a Phaseolus acutifolius Recombinant Lectin Disrupts Its Cytotoxic Activity

by
Dania Martínez-Alarcón
1,†,
José Luis Castro-Guillén
2,†,
Elaine Fitches
3,
John A. Gatehouse
3,‡,
Stefan Przyborski
3,
Ulisses Moreno-Celis
4,
Alejandro Blanco-Labra
1 and
Teresa García-Gasca
4,*
1
Centro de Investigación y de Estudios Avanzados Unidad Irapuato, Departamento de Biotecnología y Bioquímica, Irapuato 36821, Guanajuato, Mexico
2
Tecnológico Nacional de México/Instituto Tecnológico Superior de Irapuato (ITESI), Km. 12.5, Carretera Irapuato-Silao, El Copal, Irapuato 36821, Guanajuato, Mexico
3
Department of Biosciences, Durham University, Durham DH1 3LE, UK
4
Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Querétaro 76230, Querétaro, Mexico
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
This paper is dedicated to the memory of Professor John Gatehouse (1951–2022).
Int. J. Mol. Sci. 2024, 25(24), 13258; https://doi.org/10.3390/ijms252413258
Submission received: 30 September 2024 / Revised: 5 December 2024 / Accepted: 6 December 2024 / Published: 10 December 2024
(This article belongs to the Special Issue Molecular Mechanism Discovery of the Bioactive Phytochemicals against Different Diseases Based on Network Pharmacology and Molecular Docking)
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Abstract

Recently, we reported that a recombinant Tepary bean (Phaseolus acutifolius) lectin (rTBL-1) induces apoptosis in colon cancer cell lines and that cytotoxicity was related to differential recognition of β1-6 branched N-glycans. Sequencing analysis and resolution of the rTBL-1 3D structure suggest that glycan specificity could be strongly influenced by two arginine residues, R103 and R130, located in the carbohydrate binding pocket. The aim of this work was to determine the contribution of these residues towards cytotoxic activity. Two rTBL-1 mutants were produced in Pichia pastoris, biochemically characterized, and cytotoxic effects were evaluated on human colorectal cancer cells (HT-29). Substitution of either of the arginine residues with glutamines resulted in significant reductions in cytotoxic activity, with losses of 1.5 and 3 times for R103 and R130, respectively. Docking analysis showed that the mutations decreased lectin affinity binding to some Epidermal Growth Factor Receptor (EGFR)-related N-glycans. Together, these findings confirm that both of the selected arginine residues (R103 and R130) play a key role in the recognition of tumor cell glycoconjugates by rTBL-1.
Keywords: recombinant lectins; tepary bean; branched N-glycans; cancer recombinant lectins; tepary bean; branched N-glycans; cancer

Share and Cite

MDPI and ACS Style

Martínez-Alarcón, D.; Castro-Guillén, J.L.; Fitches, E.; Gatehouse, J.A.; Przyborski, S.; Moreno-Celis, U.; Blanco-Labra, A.; García-Gasca, T. Directed Mutagenesis for Arginine Substitution of a Phaseolus acutifolius Recombinant Lectin Disrupts Its Cytotoxic Activity. Int. J. Mol. Sci. 2024, 25, 13258. https://doi.org/10.3390/ijms252413258

AMA Style

Martínez-Alarcón D, Castro-Guillén JL, Fitches E, Gatehouse JA, Przyborski S, Moreno-Celis U, Blanco-Labra A, García-Gasca T. Directed Mutagenesis for Arginine Substitution of a Phaseolus acutifolius Recombinant Lectin Disrupts Its Cytotoxic Activity. International Journal of Molecular Sciences. 2024; 25(24):13258. https://doi.org/10.3390/ijms252413258

Chicago/Turabian Style

Martínez-Alarcón, Dania, José Luis Castro-Guillén, Elaine Fitches, John A. Gatehouse, Stefan Przyborski, Ulisses Moreno-Celis, Alejandro Blanco-Labra, and Teresa García-Gasca. 2024. "Directed Mutagenesis for Arginine Substitution of a Phaseolus acutifolius Recombinant Lectin Disrupts Its Cytotoxic Activity" International Journal of Molecular Sciences 25, no. 24: 13258. https://doi.org/10.3390/ijms252413258

APA Style

Martínez-Alarcón, D., Castro-Guillén, J. L., Fitches, E., Gatehouse, J. A., Przyborski, S., Moreno-Celis, U., Blanco-Labra, A., & García-Gasca, T. (2024). Directed Mutagenesis for Arginine Substitution of a Phaseolus acutifolius Recombinant Lectin Disrupts Its Cytotoxic Activity. International Journal of Molecular Sciences, 25(24), 13258. https://doi.org/10.3390/ijms252413258

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