Snake venom galactoside-binding lectins: a structural and functional overview

Sartim, Marco A.; Sampaio, Suely V.

doi:10.1186/s40409-015-0038-3

Marco A. Sartim

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto CEP 14040-903, SP, Brazil

Suely V. Sampaio ^**Corresponding author: Suely V Sampaiosuvilela@usp.br

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto CEP 14040-903, SP, Brazil

*Corresponding author: Suely V Sampaiosuvilela@usp.br

Competing interests

The authors declare that there are no competing interests.

Authors’ contributions

MAS author contributed with data compilation and writing of the manuscript. SVS contributed with supervision and critical discussion of the manuscript. Both authors read and approved the final manuscript.

Figures (3)
Tables (2)

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Fig. 1
Multiple alignment of SVgalL. The multiple alignment was performed using the program Clustal-X, and sequence similarities using ESPript 3.0 [⁷³73 . ESPript 3.0:. http://espript.ibcp.fr/ESPript/cgi-bin/ESPript.cgi
http://espript.ibcp.fr/ESPript/cgi-bin/E... ] with structure prediction based on RSL structure [PDB: 1JZN]. Fully conserved residues are highlighted in red background. Cystein residues involved in the interchain disulfide link are indicated by green numbers. Carbohydrate recognition domain (CRD) is indicated by the blue box. Primary structure according to lectins: RSL [GI: 126130], ApL [GI: 510120659], BaL [GI: 34922645], CrL [GI: 118572769], BiL [GI: 82126834], BmLec [²⁴24 . Barbosa PSF, Martins AMC, Toyama MH, Joazeiro PP, Beriam LOS, Fonteles MC et al..Purification and biological effects of a C-type lectin isolated from Bothrops moojeni.J Venom Anim Toxins incl Trop Dis. 2010; 16(3):493-504.], BpalL [GI: 527504051], BJcuL [²⁵25 . de Carvalho DD, Marangoni S, Novello JC. Primary structure characterization of Bothrops jararacussu snake venom lectin.J Protein Chem. 2002;21(1):43-50.], BpirL [GI: 510120660], LmL [GI: 1881829], ToL [²⁷27 . Nikai T, Kato S, Komori Y, Sugihara H. Amino acid sequence and biological properties of the lectin from the venom of Trimeresurus okinavensis (Himehabu). Toxicon. 2000;38(5):707-711.] and TsL [GI: 7674107]

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Fig. 2
RSL tertiary structure and carbohydrate binding site. RSL structure as described elsewhere [²²22 . Walker JR, Nagar B, Young NM, Hirama T, Rini JM. X-ray crystal structure of a galactose-specific C-type lectin possessing a novel decameric quaternary structure.Biochemistry. 2004;43(13):3783-3792.]. a A cartoon representation of the RSL dimer complexed with lactose. Cysteine side and inter chains are shown in yellow, calcium and sodium ions are represented as red and orange circles, respectively, and lactose is shown in stick representation colored in red. b Cartoon representation of the carbohydrate-binding site interacting with lactose. c Oligomerization state with the decamer viewed down the pseudo-5-fold rotation axis. The 3D structure illustration was performed using the software Pymol (The PyMOL Molecular Graphics System, Version 1.5.0.4 Schrödinger, LLC.) from RSL entry [PDB: 1jzn]

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Fig. 3
Glycan-recognition specificity. Top five glycan structures with highest binding recognition by the SVgalLs (a) RSL and (b) galatrox assessed by glycan microarray as described elsewhere [³⁴34 . Sartim MA, Riul TB, Del Cistia-Andrade C, Stowell SR, Arthur CM, Sorgi CA et al.. Galatrox is a C-type lectin in Bothrops atrox snake venom that selectively binds LacNAc-terminated glycans and can induce acute inflammation. Glycobiology. 2014;24(11):1010-1021.], [⁴²42 . Young NM, van Faassen H, Watson DC, Mackenzie CR.Specificity analysis of the C-type lectin from rattlesnake venom, and its selectivity towards Gal- or GalNAc-terminated glycoproteins.Glycoconj J. 2011;28(6):427-435.]

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Table 1
Carbohydrate inhibition specificity of SVgalLs

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Table 2
SVgalL tumoral cell lines citotoxicity

SVgalL	Snake species	Terminal galactoside carbohydrates (inhibition order)
ApL	Akgistrodon piscivorus piscivorus [¹⁵15 . Komori Y, Nikai T, Tohkai T, Sugihara H. Primary structure and biological activity of snake venom lectin (APL) from Agkistrodon p. piscivorus (Eastern cottonmouth).Toxicon. 1999;37(7):1053-1064.]	D-galactose> Lactose > N-acetyl-D-galactosamine
Thrombolectin	Bothrops atrox [⁹9 . Gartner TK, Ogilvie ML. Isolation and characterization of three Ca2 + −dependent beta-galactoside-specific lectins from snake venoms. Biochem J. 1984;224(1):301-307.]	Thiodigalactoside > Lactose > Methyl β-D-galactopyranoside > Methyl α-D-galactopyranoside > D-galactose
BiL	Bothrops insularis [¹⁶16 . Guimarães-Gomes V, Oliveira-Carvalho AL, Junqueira-de-Azevedo IL, Dutra DL S, Pujol-Luz M, Castro HC et al.. Cloning, characterization, and structural analysis of a C-type lectin from Bothrops insularis (BiL) venom. Arch Biochem Biophys. 2004;432(1):1-11.]	Thiodigalactoside > Lactose > D-galactose > N-acetyl-D-galactosamine
BjL	Bothrops jararaca [¹²12 . Ozeki Y, Matsui T, Hamako J, Suzuki M, Fujimura Y, Yoshida E et al.. C-type galactoside-binding lectin from Bothrops jararaca venom: comparison of its structure and function with those of botrocetin.Arch Biochem Biophys. 1994;308(1):306-310.]	Thiodigalactoside > Lactose = N-acetyl-lactosamine > Methyl β-D-galactoside = D-galactose > Methyl α-D-galactoside > N-acetyl-D-galactosamine
CML	Akgistrodon piscivorus leukostoma [⁹9 . Gartner TK, Ogilvie ML. Isolation and characterization of three Ca2 + −dependent beta-galactoside-specific lectins from snake venoms. Biochem J. 1984;224(1):301-307.]	Thiodigalactoside > Lactose > Methyl β-D-galactopyranoside > D-galactose > Methyl α-D-galactopyranoside
BJcuL	Bothrops jararacussu [¹⁴14 . de Carvalho DD, Marangoni S, Oliveira B, Novello JC.Isolation and characterization of a new lectin from the venom of the snake Bothrops jararacussu. IUBMB Life. 1998;44(5):933-938.]	Lactose > D-galactose > D-galactosamine
RSL	Crotalus atrox [⁹9 . Gartner TK, Ogilvie ML. Isolation and characterization of three Ca2 + −dependent beta-galactoside-specific lectins from snake venoms. Biochem J. 1984;224(1):301-307.]	Thiodigalactoside > Lactose > Methyl β-D-galactopyranoside = D-galactose > Methyl α-D-galactopyranoside
BleucL	Bothrops leucurus [²⁰20 . Nunes ES, Souza MA, Vaz AF, Santana GM, Gomes FS, Coelho LC et al.. Purification of a lectin with antibacterial activity from Bothrops leucurus snake venom. Comp Biochem Physiol B Biochem Mol Biol. 2011; 159(1):57-63.]	D-galactose > Lactose > N-acetyl-D-glucosamine > asialofetuin
BpaL	Bothrops pauloensis [²¹21 . Castanheira LE, Nunes DC, Cardoso TM, Santos PS, Goulart LR, Rodrigues RS et al..Biochemical and functional characterization of a C-type lectin (BpLec) from Bothrops pauloensis snake venom.Int J Biol Macromol. 2013;54:57-64. ]	Lactose > D-galactose > N-acetyl-D-galactosamine
BpL	Bothrops pirajai [¹⁷17 . Havt A, Toyama MH, do Nascimento NR, Toyama DO, Nobre AC, Martins AM et al.. A new C-type animal lectin isolated from Bothrops pirajai is responsible for the snake venom major effects in the isolated kidney.Int J Biochem Cell Biol. 2005;37(1):130-141.]	Lactose > D-galactose
CuHL	Akgistrodon contortrix contortrix [⁹9 . Gartner TK, Ogilvie ML. Isolation and characterization of three Ca2 + −dependent beta-galactoside-specific lectins from snake venoms. Biochem J. 1984;224(1):301-307.]	Thiodigalactoside > Methyl β-D-galactopyranoside > Lactose > Methyl α-D-galactopyranoside > D-galactose
CrL	Crotalus ruber [¹⁸18 . Hamako J, Suzuki Y, Hayashi N, Kimura M, Ozeki Y, Hashimoto K et al.. Amino acid sequence and characterization of C-type lectin purified from the snake venom of Crotalus ruber. Comp Biochem Physiol B Biochem Mol Biol. 2007;146(3):299-306.]	Thiodigalactoside > N-acetyl-D-galactosamine = Lactulose > Lactose = Methyl β-D-galactoside > D-galactose
LmL	Lachesis muta stenophyrs [¹⁰10 . Ogilvie ML, Dockter ME, Wenz L, Gartner TK. Isolation and characterization of lactose-binding lectins from the venoms of the snakes Lachesis muta and Dendroaspis jamesonii. J Biochem. 1986; 100(6):1425-1431.]	Thiodigalactoside > Lactose > Methyl β D-galactopyranoside > D-galactose > Methyl α D-galactopyranoside > Galactosamine
ToL	Trimeresurus okinavensis [²⁷27 . Nikai T, Kato S, Komori Y, Sugihara H. Amino acid sequence and biological properties of the lectin from the venom of Trimeresurus okinavensis (Himehabu). Toxicon. 2000;38(5):707-711.]	Thiodigalactoside = Lactose
JML	Dendroaspis jamesonii [¹⁰10 . Ogilvie ML, Dockter ME, Wenz L, Gartner TK. Isolation and characterization of lactose-binding lectins from the venoms of the snakes Lachesis muta and Dendroaspis jamesonii. J Biochem. 1986; 100(6):1425-1431.]	Thiodigalactoside = Lactose > Methyl α D-galactoside > Metyl β D-galactoside > D-galactose > Galactosamine

SVgalL	Snake venom specie (reference)	Tumorigenic cell line
Galatrox	Bothrops atrox [¹⁹19 . Mendonça-Franqueiro EP, Alves-Paiva RM, Sartim MA, Callejon DR, Paiva HH, Antonucci GA et al.. Isolation, functional, and partial biochemical characterization of galatrox, an acidic lectin from Bothrops atrox snake venom. Acta Biochim Biophys Sin. 2011;43(3):181-192.]	HL-60 (human promyelocytic leukemia)
BJcuL	Bothrops jararacussu [⁶⁸68 . Nolte S, de Castro DD, Baréa AC, Gomes J, Magalhães A, Mello Zischler LF et al.. BJcuL, a lectin purified from Bothrops jararacussu venom, induces apoptosis in human gastric carcinoma cells accompanied by inhibition of cell adhesion and actin cytoskeleton disassembly.Toxicon. 2012; 59(1):81-85., ⁶⁹69 . Damasio DC, Nolte S, Polak LP, Brandt AP, Bonan NB, Zischler L et al.. The lectin BJcuL induces apoptosis through TRAIL expression, caspase cascade activation and mitochondrial membrane permeability in a human colon adenocarcinoma cell line.Toxicon. 2014;90:299-307., ⁷⁴74 . de Carvalho DD, Schmitmeier S, Novello JC, Markland FS.Effect of BJcuL (a lectin from the venom of the snake Bothrops jararacussu) on adhesion and growth of tumor and endothelial cells.Toxicon. 2001;39(10):1471-1476.]	MDA-MB- 435 (human breast carcinoma); OVCAR-5 (ovarian carcinoma); U87 and A-172 (glioblastoma); MKN45 and AGS (human gastric carcinoma); HT29 (human colon adenocarcinoma)
BleucL	Bothrops leucurus [⁷⁰70 . Nunes ES, Souza MA, Vaz AF, Silva TG, Aguiar JS, Batista AM et al.. Cytotoxic effect and apoptosis induction by Bothrops leucurus venom lectin on tumor cell lines. Toxicon. 2012;59(7–8):667-671., ⁷²72 . Aranda-Souza MA, Rossato FA, Costa RA, Figueira TR, Castilho RF, Guarniere MC et al.. A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition. Toxicon.2014; 82:97-103.]	K562 (human chronic myelocytic leukemia); NCI-H292 (human lung mucoepidermoid carcinoma); Hep-2 (human larynx epidermoid carcinoma); B16-F10 (melanoma)

[1] *Corresponding author: Suely V Sampaiosuvilela@usp.br

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Snake venom galactoside-binding lectins: a structural and functional overview

Abstract