Exploration of carbohydrate binding behavior and anti-proliferative activities of Arisaema tortuosum lectin
Tóm tắt
Lectins have come a long way from being identified as proteins that agglutinate cells to promising therapeutic agents in modern medicine. Through their specific binding property, they have proven to be anti-cancer, anti-insect, anti-viral agents without affecting the non-target cells. The Arisaema tortuosum lectin (ATL) is a known anti-insect and anti-cancer candidate, also has interesting physical properties. In the present work, its carbohydrate binding behavior is investigated in detail, along with its anti-proliferative property. The microcalorimetry of ATL with a complex glycoprotein asialofetuin demonstrated trivalency contributed by multiple binding sites and enthalpically driven spontaneous association. The complex sugar specificity of ATL towards multiple sugars was also demonstrated in glycan array analysis in which the trimannosyl pentasaccharide core N-glycan [Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ] was the highest binding motif. The high binding glycans for ATL were high mannans, complex N-glycans, core fucosylated N-glycans and glycans with terminal lactosamine units attached to pentasaccharide core. ATL induced cell death in IMR-32 cells was observed as time dependent loss in cell number, formation of apoptotic bodies and DNA damage. As a first report of molecular cloning of ATL, the in silico analysis of its cDNA revealed ATL to be a β-sheet rich heterotetramer. A homology model of ATL showed beta prism architecture in each monomer with 85% residues in favoured region of Ramachandran plot. Detailed exploration of carbohydrate binding behavior indicated ATL specificity towards complex glycans, while no binding to simple sugars, including mannose. Sequence analysis of ATL cDNA revealed that during the tandem evolutionary events, domain duplication and mutations lead to the loss of mannose specificity, acquiring of new sugar specificity towards complex sugars. It also resulted in the formation of a two-domain single chain polypeptide with both domains having different binding sites due to mutations within the consensus carbohydrate recognition sites [QXDXNXVXY]. This unique sugar specificity can account for its significant biological properties. Overall finding of present work signifies anti-cancer, anti-insect and anti-viral potential of ATL making it an interesting molecule for future research and/or theragnostic applications.
Tài liệu tham khảo
Ghazarian H, Idoni B, Oppenheimer SB. A glycobiology review: carbohydrates, lectins and implications in cancer therapeutics. Acta Histochem. 2011;113:236–47.
Christiansen MN, Chik J, Lee L, Anugraham M, Abrahams JL, Packer NH. Cell surface protein glycosylation in cancer. Proteomics. 2014;14:525–46.
Ho WL, Hsu WM, Huang MC, Kadomatsu K, Nakagawara A. Protein glycosylation in cancers and its potential therapeutic applications in neuroblastoma. J Hematol Oncol. 2016;9:100.
Pearce OM. Cancer glycan epitopes: biosynthesis, structure, and function. Glycobiology. 2018;28:670–96.
Liu Z, Luo Y, Zhou TT, Zhang WZ. Could plant lectins become promising anti-tumour drugs for causing autophagic cell death? Cell Prolif. 2013;46:509–15.
Mukhopadhyay S, Panda PK, Behera B, Das CK, Hassan MK, Das DN, et al. In vitro and in vivo antitumor effects of Peanut agglutinin through induction of apoptotic and autophagic cell death. Food Chem Toxicol. 2014;64:369–77.
Jiang QL, Zhang S, Tian M, Zhang SY, Xie T, Chen DY, et al. Plant lectins, from ancient sugar-binding proteins to emerging anti-cancer drugs in apoptosis and autophagy. Cell Prolif. 2015;48:17–28.
Kabir SR, Nabi MM, Nurujjaman M, Abu Reza M, Alam AH, Uz Zaman R, et al. Momordica charantia seed lectin: toxicity, bacterial agglutination and antitumor properties. Appl Biochem Biotechnol. 2015;175:2616–28.
Marvibaigi M, Supriyanto E, Amini N, Majid AFA, Jaganathan SK. Preclinical and clinical effects of mistletoe against breast cancer. Biomed Res Int. 2014;2014:1–15.
Inamdar SR, Eligar SM, Ballal S, Belur S, Kalraiya RD, Swamy BM. Exquisite specificity of mitogenic lectin from Cephalosporium curvulum to core fucosylated N-glycans. Glycoconj J. 2016;33:19–28.
Van Damme EJM. History of plant lectin research. In: Hirabayashi J, editor. Lectins: methods and protocols. Springer Science: New York; 2014. p. 3–13.
Luo Y, Xu X, Liu J, Li J, Sun Y, Liu Z, et al. A novel mannose-binding tuber lectin from Typhonium divaricatum (L.) Decne (family Araceae) with antiviral activity against HSV-II and anti-proliferative effect on human cancer cell lines. J Biochem Mol Biol. 2007;40:358–67.
Macedo MLR, Oliveira CFR, Oliveira CT. Insecticidal activity of plant lectins and potential application in crop protection. Molecules. 2015;20:2014–33.
Thakur K, Kaur M, Kaur S, Kaur A, Kamboj SS, Singh J. Purification of Colocasia esculenta and determination of its anti-insect potential towards Bactrocera cucurbitae. J Environ Biol. 2013;34:31–6.
Kaur M, Thakur K, Kamboj SS, Kaur S, Kaur A, Singh J. Assessment of Sauromatum guttatum lectin toxicity against Bactrocera cucurbitae. J Environ Biol. 2015;36:1263–8.
Boyce PC, Croat TB. The Uberlist of Araceae, totals for published and estimated number of species in aroid genera. 2011 onwards. http://www.aroid.org/genera/160330uberlist.pdf. Accessed 1 Sept 2018.
Kaur M, Singh K, Rup PJ, Saxena AK, Khan RH, Ashraf MT, et al. A tuber lectin from Arisaema helliborifolium Schott. with anti-insect activity against melon fruit fly Bactrocera cucurbitae (Coquillett) and anticancer effect on human cancer cell lines. Arch Biochem Biophys. 2006;445:156–65.
Thakur K, Kaur M, Rabbani G, Khan RH, Singh S, Singh J. Structural variations and molten globule state in Arisaema helliborifolium lectin under various treatments as monitored by spectroscopy. Protein Pept Lett. 2016;23:107–19.
Ramachandraiah G, Chandra NR. Sequence and structural determinants of mannose recognition. Proteins. 2000;39:358–64.
Ogata M, Chuma Y, Yasumoto Y, Onoda T, Umemura M, Usui T, et al. Synthesis of tetravalent LacNAc-glycoclusters as high-affinity cross-linker against Erythrina cristagalli agglutinin. Bioorg Med Chem. 2016;24:1–11.
Thakur K, Kaur T, Singh J, Rabbani G, Khan RH, Hora R, et al. Sauromatum guttatum lectin: spectral studies, lectin–carbohydrate interaction, molecular cloning and in silico analysis. Int J Biol Macromol. 2017;104:1267–79.
Dam TK, Roy R, Das SK, Oscarson S, Brewer CF. Binding of multivalent carbohydrates to concanavalin A and Dioclea grandiflora lectin. Thermodynamic analysis of the “multivalency effect”. J Biol Chem. 2000;275:14223–30.
Mizuochi T, Spellman MW, Larkin M, Solomon J, Basa LJ, Feizi T. Carbohydrate structures of the human-immunodeficiency-virus (HIV) recombinant envelope glycoprotein gp120 produced in Chinese-hamster ovary cells. Biochem J. 1988;254:599–603.
Kui Wong N, Easton RL, Panico M, Sutton-Smith M, Morrison JC, Lattanzio FA, et al. Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125. J Biol Chem. 2003;278:28619–34.
Goetz JA, Mechref Y, Kang P, Jeng MH, Novotny MV. Glycomic profiling of invasive and non-invasive breast cancer cells. Glycoconj J. 2009;26:117–31.
Jacob F, Goldstein DR, Bovin NV, Pochechueva T, Spengler M, Caduff R, et al. Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array. Int J Cancer. 2012;130:138–46.
Schachter H. Paucimannose N-glycans in Caenorhabditis elegans and Drosophila melanogaster. Carbohydr Res. 2009;344:1391–6.
Tiemeyer M, Selleck SB, Esko JD. Arthropoda. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME, editors. Essentials of glycobiology. New York: Cold Spring Harbor; 2009.
Gambaryan AS, Tuzikov AB, Piskarev VE, Yamnikova SS, Lvov DK, Robertson JS, et al. Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and influenza B viruses share a common high binding affinity for 6′-sialyl (N-acetyllactosamine). Virology. 1997;232:345–50.
Potapenko IO, Haakensen VD, Luders T, Helland A, Bukholm I, Sorlie T, et al. Glycan gene expression signatures in normal and malignant breast tissue; possible role in diagnosis and progression. Mol Oncol. 2010;4:98–118.
Miyoshi E, Moriwaki K, Terao N, Tan CC, Terao M, Nakagawa T, et al. Fucosylation is a promising target for cancer diagnosis and therapy. Biomolecules. 2012;2:34–45.
Golijanin D, Sherman Y, Shapiro A, Pode D. Detection of bladder tumors by immunostaining of the Lewis X antigen in cells from voided urine. Urology. 1995;46:173–7.
Barthel SR, Gavino JD, Descheny L, Dimitroff CJ. Targeting selectins and selectin ligands in inflammation and cancer. Expert Opin Ther Targets. 2007;11:1473–91.
Qasba PK, Ramakrishnan B, Boeggeman E. Structure and function of β-1,4-galactosyltransferase. Curr Drug Targets. 2008;9:292–309.
Chen CH, Wang SH, Liu CH, Wu YL, Wang WJ, Huang J, et al. β-1,4-Galactosyltransferase III suppresses β1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer. Carcinogenesis. 2014;35:1258–66.
Van Damme EJM, Nakamura-Tsurata S, Smith D, Ongenaert M, Winter H, Rouge P, et al. Phylogenetic and specificity studies of two-domain GNA-related lectins: generation of multispecificity through domain duplication and divergent evolution. Biochem J. 2007;404:51–61.
Shetty KN, Ganapati G, Bhat GG, Inamdar SR, Swamy BM, Suguna K. Crystal structure of a β-prism II lectin from Remusatia vivipara. Glycobiology. 2012;22:56–69.
Sharma A, Chandran D, Singh DD, Vijayan M. Multiplicity of carbohydrate-binding sites in β-prism fold lectins: occurrence and possible evolutionary implications. J Biosci. 2007;32:1089–110.
Ramachandraiah G, Chandra NR, Surolia A, Vijayan M. Computational analysis of multivalency in lectins: structures of garlic lectin–oligosaccharide complexes and their aggregates. Glycobiology. 2003;13:765–75.
Nakagawa Y, Sakamoto H, Tateno H, Hirabyashi J, Oguri S. Purification, characterization and molecular cloning of lectin from winter buds of Lysichiton camtschatcensis (L.) Schott. Biosci Biotechnol Biochem. 2012;76:25–33.
Boix J, Llecha N, Yuste VJ, Comella JX. Characterization of the cell death process induced by staurosporine in human neuroblastoma cell lines. Neuropharmacology. 1997;36:811–21.
Yuste VJ, Bayascas JR, Llecha N, Sanchez-Lopez I, Boix J, Comella JX. The absence of oligonucleosomal DNA fragmentation during apoptosis of IMR-5 neuroblastoma cells: disappearance of the caspase-activated DNase. J Biol Chem. 2001;276:22323–31.
Blixt O, Head S, Mondala T, Scanlan C, Huflejt ME, Alvarez R, et al. Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc Natl Acad Sci USA. 2004;101:17033–8.
Agravat SB, Saltz JH, Cummings RD, Smith DF. GlycoPattern: a web platform for glycan array mining. Bioinformatics. 2014;30:3417–8.
Smith DF, Song X, Cummings RD. Use of glycan microarrays to explore specificity of glycan-binding proteins. In: Burlington FM, editor. Methods in enzymology. New York: Academic Press Inc; 2010. p. 417–44.
Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018;35:1547–9.
Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987;4:406–25.
Nei M, Kumar S. Molecular evolution and phylogenetics. New York: Oxford University Press; 2000.
Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993;234:779–815.
Bhattacharya D, Cheng J. 3Drefine: consistent protein structure refinement by optimizing hydrogen bonding network and atomic-level energy minimization. Proteins. 2013;81:119–31.
Sambrook J, Russel DR. Molecular cloning: a laboratory manual. NewYork: Cold Spring Harbor Laboratory Press; 2001.