In Silico Analysis of Lentil Concanavalin a Interaction with Human ALDH18A1: Implications for Pediatric Gastrointestinal Cancers and Encephalopathy

Document Type : Research Paper

Authors

1 Department of Pediatrics, School of Medicine, Amir al momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran

2 Department of Pathology, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran

3 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

4 Department of Agronomy and Plant Breeding, Agriculture Institute, Research Institute of Zabol, Zabol, Iran

Abstract

Pediatric gastrointestinal cancers, although rare, can be accompanied by neurological manifestations such as encephalopathy. The human ALDH18A1 gene, which plays a pivotal role in proline biosynthesis and mitochondrial function, is considered a key contributor to these complications. On the other hand, Concanavalin A (ConA), a plant-derived lectin capable of binding to cell-surface carbohydrates, is known for its anti-tumor and regulatory properties. This study aimed to investigate the potential structural and functional interaction between ConA and ALDH18A1 using bioinformatics tools including BLASTp, ClusPro, PyMOL, and QMEAN. Protein sequences were retrieved from the UniProt database. Sequence homology was analyzed via BLASTp, and three-dimensional structures were obtained from the Protein Data Bank (PDB). Protein–protein docking simulations were performed using the ClusPro server, and the results were analyzed with PyMOL. Despite low sequence similarity (<25% identity, E-value> 0.01 based on BLASTp results) between the two proteins (Zero), docking analysis revealed that Cluster 9, with a binding energy of −1023.5 (arbitrary units as defined by ClusPro), represented the most stable interaction model between ConA and ALDH18A1. Structural analysis Confirmed stable spatial contacts, including hydrogen bonds and electrostatic attractions, particularly between charged/polar residues such as between the functional domains of the two proteins. This study suggests that the molecular interaction between ConA and ALDH18A1 may influence cancer-related and neurological pathways through structure-based mechanisms involving domain–domain interaction and electrostatic complementarity, rather than sequence-based homology. These findings suggest specific avenues for future research, including SPR binding assays and mutagenesis, to validate the predicted interaction experimentally. Understanding this interaction could inform therapeutic strategies targeting metabolic dysfunction in pediatric cancer patients with neurological symptoms. This interaction may disrupt ALDH18A1-associated amino acid metabolism, which plays a role in neuronal homeostasis and could contribute to the development of encephalopathy. This study is computational in nature and lacks experimental validation, which is a key limitation to be addressed in future research.

Keywords

Main Subjects

References

  1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68(6): 394-424.
  2. Parissis D., Dimitriou M., Ioannidis P. Genetic causes of acute encephalopathy in adults: beyond inherited metabolic and epileptic disorders. Neurological Sciences. 2022; 43(3): 1617-1626.
  3. Li P., Wu G. Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth. Amino Acids. 2018; 50(1): 29-38.
  4. Bae Y.S., Yoon S.H., Han J.Y., Woo J., Cho Y.S., Kwon S.K., Bae Y.C., Kim D., Kim E., Kim M.H. Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration. Genes Brain Behav. 2018; 17(2): 126-138.
  5. Yu L.G. The oncofetal Thomsen-Friedenreich carbohydrate antigen in cancer progression. Glycoconjugate Journal. 2007; 24(8): 411-420.
  6. Li W.W., Yu J.Y., Xu H.L., Bao J.K. Concanavalin A: a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics. Biochemical and Biophysical Research Communications. 2011; 414(2): 282-286.
  7. Yalcin G.D., Danisik N., Baygin R.C., Acar A. Systems Biology and Experimental Model Systems of Cancer. Journal of Personalized Medicine. 2020; 10(4).
  8. Floyd B.J., Wilkerson E.M., Veling M.T., Minogue C.E., Xia C., Beebe E.T., Wrobel R.L., Cho H., Kremer L.S., Alston C.L., Gromek K.A., Dolan B.K., Ulbrich A., Stefely J.A., Bohl S.L., Werner K.M., Jochem A., Westphall M.S., Rensvold J.W., Taylor R.W., Prokisch H., Kim J.P., Coon J.J., Pagliarini D.J. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Molecular Cell. 2016; 63(4): 621-632.
  9. The-UniProt-Consortium. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Research. 2021; 49(D1): D480-d489.
  10. Altschul S.F., Gish W., Miller W., Myers E.W., Lipman D.J. Basic local alignment search tool. Journal of Molecular Biology. 1990; 215(3): 403-410.
  11. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., Shindyalov I.N., Bourne P.E. The protein data bank. Nucleic Acids Research. 2000; 28(1): 235-242.
  12. Kozakov D., Hall D.R., Xia B., Porter K.A., Padhorny D., Yueh C., Beglov D., Vajda S. The ClusPro web server for protein-protein docking. Nature Protocols. 2017; 12(2): 255-278.
  13. Vajda S., Yueh C., Beglov D., Bohnuud T., Mottarella S.E., Xia B., Hall D.R., Kozakov D. New additions to the ClusPro server motivated by CAPRI. Proteins. 2017; 85(3): 435-444.
  14. Huldani H., Rashid A.I., Turaev K.N., Opulencia M.J.C., Abdelbasset W.K., Bokov D.O., Mustafa Y.F., Al-Gazally M.E., Hammid A.T., Kadhim M.M., Ahmadi S.H. Concanavalin A as a promising lectin-based anti-cancer agent: the molecular mechanisms and therapeutic potential. Cell Communication and Signaling. 2022; 20(1): 167.
  15. Komachali S.R., Siahpoosh Z., Salehi M. Two novel mutations in ALDH18A1 and SPG11 gene found by whole-exome sequencing in spastic paraplegia disease patients in Iran. Genomics & Informatics. 2022; 20(3): e30.
  16. Laskowski R.A., MacArthur M.W., Moss D.S., Thornton J.M. PROCHECK: a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography. 1993; 26(2): 283-291.
  17. Benkert P., Biasini M., Schwede T. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics. 2011; 27(3): 343-350.
  18. Chen V.B., Arendall W.B., Headd J.J., Keedy D.A., Immormino R.M., Kapral G.J., Murray L.W., Richardson J.S., Richardson D.C. MolProbity: all-atom structure validation for macromolecular crystallography. Biological Crystallography. 2010; 66(1): 12-21.
  19. Studer G., Rempfer C., Waterhouse A.M., Gumienny R., Haas J., Schwede T. QMEANDisCo—distance constraints applied on model quality estimation. Bioinformatics. 2020; 36(6): 1765-1771.
  20. Comeau S.R., Gatchell D.W., Vajda S., Camacho C.J. ClusPro: a fully automated algorithm for protein-protein docking. Nucleic Acids Research. 2004; 32(Web Server issue): W96-99.
  21. Chen C., Zhang Q., Wang B., Song Y., Feng Z., Ren S. SPTBN2 regulated by miR-214-3p inhibits the proliferation and migration of colorectal cancer cells: SPTBN2 inhibits the colorectal cancer cells. Cellular and Molecular Biology. 2023; 69(14): 126-131.
  22. Sun G., Gong S., Lan S., He Y., Sun Y., Zhang Z. TMCO1 regulates cell proliferation, metastasis and EMT signaling through CALR, promoting ovarian cancer progression and cisplatin resistance: TMCO1 promotes ovarian cancer and cisplatin resistance. Cellular and Molecular Biology. 2024; 70(1): 99-109.
Journal of Medicinal plants and By-products
Volume 15, Issue 1
January and February 2026
Pages 132-138

Files

Share

How to cite

Statistics