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Surface Topology Evolution of Trypanosoma Trans-Sialidase

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Book cover Proteins and Proteomics of Leishmania and Trypanosoma

Part of the book series: Subcellular Biochemistry ((SCBI,volume 74))

Abstract

The trans-sialidase (TS) from Trypanosoma cruzi is a multifunctional protein given by its enzymatic activity and binding properties. The complex structure of TS promotes topology changes over the protozoa’s surface with dramatic consequences for its biology. Detailed sequence analyses show that the evolution of TS in T. cruzi and other trypanosomes as well as its genomic organization is even more complex than it has been supposed before. All of these aspects are still neglected when TS is selected as a target for drug design and chemotherapy of Chagas’ disease. Herein these aspects are discussed in the context of TS multifunctionality and dynamics drug design.

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Abbreviations

GH-33:

Glycoside hydrolase family number 33

GPI:

Glycosylphosphatidylinositol

MDS:

Multidimensional scaling plot

SAPA:

Shed Acute Phase Antigen

TS:

Trans-Siliadase

TS342His/− :

Inactive Trans-Siliadase without SAPA

TS342His/SAPA :

Inactive Trans-Siliadase with SAPA

TS342Tyr/− :

Active Trans-Siliadase without SAPA

TS342Tyr/SAPA :

Active Trans-Siliadase with SAPA

References

  • Affranchino JL, Ibanez CF, Luquetti AO et al (1989) Identification of a Trypanosoma cruzi antigen that is shed during the acute phase of Chagas’ disease. Mol Biochem Parasitol 3:221–228

    Article  Google Scholar 

  • Aguero F, Campo V, Cremona L et al (2002) Gene discovery in the freshwater fish parasite Trypanosoma carassii: identification of trans-sialidase-like and mucin-like genes. Infect Immun 12:7140–7144

    Article  Google Scholar 

  • Agusti R, Couto AS, Campetella OE et al (1997) The trans-sialidase of Trypanosoma cruzi is anchored by two different lipids. Glycobiology 6:731–735

    Article  Google Scholar 

  • Agusti R, Couto AS, Campetella O et al (1998) Structure of the glycosylphosphatidylinositol-anchor of the trans-sialidase from Trypanosoma cruzi metacyclic trypomastigote forms. Mol Biochem Parasitol 1–2:123–131

    Article  Google Scholar 

  • Agusti R, Paris G, Ratier L et al (2004) Lactose derivatives are inhibitors of Trypanosoma cruzi trans- sialidase activity toward conventional substrates in vitro and in vivo. Glycobiology 7:659–670

    Article  Google Scholar 

  • Alves MJ, Colli W (2008) Role of the gp85/trans-sialidase superfamily of glycoproteins in the interaction of Trypanosoma cruzi with host structures. Subcell Biochem 47:58–69

    Article  PubMed  Google Scholar 

  • Amino R, Porto RM, Chammas R et al (1998) Identification and characterization of a sialidase released by the salivary gland of the hematophagous insect Triatoma infestans. J Biol Chem 38:24575–24582

    Article  Google Scholar 

  • Arioka S, Sakagami M, Uematsu R et al (2010) Potent inhibitor scaffold against Trypanosoma cruzi trans-sialidase. Bioorg Med Chem 4:1633–1640

    Article  Google Scholar 

  • Aslett M, Aurrecoechea C, Berriman M et al (2010) Tritrypdb: a functional genomic resource for the trypanosomatidae. Nucleic Acids Res 38:D457–D462

    Article  PubMed  CAS  Google Scholar 

  • Atwood JA III, Weatherly DB, Minning TA et al (2005) The Trypanosoma cruzi proteome. Science 5733:473–476

    Article  Google Scholar 

  • Beucher M, Norris KA (2008) Sequence diversity of the Trypanosoma cruzi complement regulatory protein family. Infect Immun 2:750–758

    Article  Google Scholar 

  • Briones MRS, Egima CM, Acosta A et al (1994) Trans-sialidase and sialic acid acceptors from insect to ammalian stages of Trypanosoma cruzi. Exp Parasitol 79:211–214

    Article  PubMed  CAS  Google Scholar 

  • Briones MRS, Egima CM, Eichinger D et al (1995a) Trans-sialidase genes expressed in mammalian forms of Trypanosoma cruzi evolved from an ancestor gene expressed in insect forms of the parasite. J Mol Evol 41:120–131

    Google Scholar 

  • Briones MRS, Egima CM, Schenkman S (1995b) Trypanosoma cruzi trans-sialidase gene lacking C-terminal repeats and expressed in epimastigote forms. Mol Biochem Parasitol 70:9–17

    Article  PubMed  CAS  Google Scholar 

  • Bua J, Garcia GA, Galindo M et al (1999) Trypanosoma cruzi genome: transcriptional mapping and karyotype correlation; molecular characterization of a surface antigen from the TC13 family. Medicina 59(suppl 2):11–17

    Google Scholar 

  • Buchini S, Buschiazzo A, Withers SG (2008) A new generation of specific Trypanosoma cruzi trans-sialidase inhibitors. Angew Chem 14:2700–2703

    Google Scholar 

  • Buscaglia CA, Alfonso J, Campetella O et al (1999) Tandem amino acid repeats from Trypanosoma cruzi shed antigens increase the half-life of proteins in blood. Blood 6:2025–2032

    Google Scholar 

  • Buscaglia CA, Campo VA, Frasch AC et al (2006) Trypanosoma cruzi surface mucins: host-dependent coat diversity. Nat Rev Microbiol 3:229–236

    Article  Google Scholar 

  • Buschiazzo A, Cremona ML, Campetella O et al (1993) Sequence of a Trypanosoma rangeli gene closely related to Trypanosoma cruzi trans-sialidase. Mol Biochem Parasitol 62:115–116

    Article  PubMed  CAS  Google Scholar 

  • Buschiazzo A, Amaya MF, Cremona ML et al (2002) The crystal structure and mode of action of trans-sialidase, a key enzyme in Trypanosoma cruzi pathogenesis. Mol Cell 4:757–768

    Article  Google Scholar 

  • Buschiazzo A, Muia R, Larrieux N et al (2012) Trypanosoma cruzi trans-sialidase in complex with a neutralizing antibody: structure/function studies towards the rational design of inhibitors. PLoS Pathog 1:e1002474

    Article  Google Scholar 

  • Campetella O, Sanchez D, Cazzulo JJ et al (1992) A superfamily of Trypanosoma cruzi surface antigens. Parasitol Today 11:378–381

    Article  Google Scholar 

  • Campetella OE, Uttaro AD, Parodi AJ et al (1994) A recombinant Trypanosoma cruzi trans-sialidase lacking the amino acid repeats retains the enzymatic activity. Mol Biochem Parasitol 64:337–340

    Article  PubMed  CAS  Google Scholar 

  • Campo VL, Sesti-Costa R, Carneiro ZA et al (2012) Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase. Bioorg Med Chem 1:145–156

    Article  Google Scholar 

  • Carvalho I, Andrade P, Campo VL et al (2010a) ‘Click chemistry’ synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against Trypanosoma cruzi and its cell surface trans-sialidase. Bioorg Med Chem 7:2412–2427

    Article  Google Scholar 

  • Carvalho ST, Sola-Penna M, Oliveira IA et al (2010b) A new class of mechanism-based inhibitors for Trypanosoma cruzi trans-sialidase and their influence on parasite virulence. Glycobiology 8:1034–1045

    Article  Google Scholar 

  • Cazzulo JJ, Frasch ACC (1992) Sapa/trans-sialidase and cruzipain: two antigens from Trypanosoma cruzi contain immunodominant but enzymatically inactive domains. FASEB J 6:3259–3264

    PubMed  CAS  Google Scholar 

  • Chaves LB, Briones MRS, Schenkman S (1993) Trans-sialidase from Trypanosoma cruzi epimastigotes is expressed at the stationary phase and is different from the enzyme expressed in trypomastigotes. Mol Biochem Parasitol 1:97–106

    Article  Google Scholar 

  • Chuenkova MV, PereiraPerrin M (2005) A synthetic peptide modeled on pdnf, Chagas’ disease parasite neurotrophic factor, promotes survival and differentiation of neuronal cells through TrkA receptor. Biochemistry 48:15685–15694

    Article  Google Scholar 

  • Cremona ML, Sanchez DO, Frasch ACC et al (1995) A single tyrosine differentiates active and inactive Trypanosoma cruzi trans-sialidases. Mol Biochem Parasitol 160:123–128

    CAS  Google Scholar 

  • Cremona ML, Campetella O, Sanchez DO et al (1999) Enzymically inactive members of the trans-sialidase family from Trypanosoma cruzi display beta-galactose binding activity. Glycobiology 6:581–587

    Google Scholar 

  • Cross GA, Takle GB (1993) The surface trans-sialidase family of Trypanosoma cruzi. Annu Rev Microbiol 1:385–411

    Article  Google Scholar 

  • Dc-Rubin SS, Schenkman S (2012) Trypanosoma cruzi trans-sialidase as a multifunctional enzyme in Chagas’ disease. Cell Microbiol 10:1522–1530

    Article  Google Scholar 

  • Egima CM, Briones MRS, Freitas-Junior LHG et al (1996) Organization of trans-sialidase genes in Trypanosoma cruzi. Mol Biochem Parasitol 77:115–125

    Article  PubMed  CAS  Google Scholar 

  • El-Sayed NM, Myler PJ, Bartholomeu DC et al (2005) The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 5733:409–415

    Article  Google Scholar 

  • Frasch ACC (1994) Trans-sialidases in the insect-vector stages of African and American trypanosomes. Parasitol Today 10:170–171

    Article  PubMed  CAS  Google Scholar 

  • Frasch AC (2000) Functional diversity in the trans-sialidase and mucin families in Trypanosoma cruzi. Parasitol Today 7:282–286

    Article  Google Scholar 

  • Freitas LM, dos Santos SL, Rodrigues-Luiz GF et al (2011) Genomic analyses, gene expression and antigenic profile of the trans-sialidase superfamily of Trypanosoma cruzi reveal an undetected level of complexity. PLoS One 10:e25914

    Article  Google Scholar 

  • Garcia ES, Azambuja P (1991) Development and interactions of Trypanosoma cruzi within the insect vector. Parasitol Today 7:240–244

    Article  PubMed  CAS  Google Scholar 

  • Giorgi ME, Ratier L, Agusti R et al (2010) Synthesis of pegylated lactose analogs for inhibition studies on Trypanosoma cruzi trans-sialidase. Glycoconj J 5:549–559

    Article  Google Scholar 

  • Henrissat B, Bairoch A (1996) Updating the sequence-based classification of glycosyl hydrolases. Biochem J 2:695–696

    Google Scholar 

  • Jager AV, Muia RP, Campetella O (2008) Stage-specific expression of Trypanosoma cruzi trans- sialidase involves highly conserved 3′ untranslated regions. FEMS Microbiol Lett 2:182–188

    Article  Google Scholar 

  • Kim D, Chiurillo MA, El-Sayed N et al (2005) Telomere and subtelomere of Trypanosoma cruzi chromosomes are enriched in (pseudo)genes of retrotransposon hot spot and trans-sialidase-like gene families: the origins of T. cruzi telomeres. Gene 346:153–161

    Google Scholar 

  • Kim JH, Ryu HW, Shim JH et al (2009) Development of new and selective Trypanosoma cruzi trans-sialidase inhibitors from sulfonamide chalcones and their derivatives. Chembiochem 15:2475–2479

    Article  Google Scholar 

  • Koliwer-Brandl H, Gbem TT, Waespy M et al (2011) Biochemical characterization of trans-sialidase TS1 variants from Trypanosoma congolense. BMC Biochem 1:39

    Google Scholar 

  • Lewis AL, Desa N, Hansen EE et al (2009) Innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structure. Proc Natl Acad Sci USA 32:13552–13557

    Article  Google Scholar 

  • Lieke T, Grobe D, Blanchard V et al (2011) Invasion of Trypanosoma cruzi into host cells is impaired by N-propionylmannosamine and other N-acylmannosamines. Glycoconj J 1:31–37

    Article  Google Scholar 

  • Meinke S, Schroven A, Thiem J (2011) Sialic acid c-glycosides with aromatic residues: investigating enzyme binding and inhibition of Trypanosoma cruzi trans-sialidase. Org Biomol Chem 9(12):4487–4497

    Article  PubMed  CAS  Google Scholar 

  • Montagna G, Cremona ML, Paris G et al (2002) The trans-sialidase from the African trypanosome Trypanosoma brucei. Eur J Biochem 12:2941–2950

    Article  Google Scholar 

  • Neres J, Bonnet P, Edwards PN et al (2007) Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase. Bioorg Med Chem 5:2106–2119

    Article  Google Scholar 

  • Neres J, Brewer ML, Ratier L et al (2009) Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening. Bioorg Med Chem Lett 3:589–596

    Article  Google Scholar 

  • Paris G, Ratier L, Amaya MF et al (2005) A sialidase mutant displaying trans-sialidase activity. J MolBiol 4:923–934

    Article  Google Scholar 

  • Pitcovsky TA, Mucci J, Alvarez P et al (2001) Epitope mapping of trans-sialidase from Trypanosoma cruzi reveals the presence of several cross-reactive determinants. Infect Immun 3:1869–1875

    Article  Google Scholar 

  • Pitcovsky TA, Buscaglia CA, Mucci J et al (2002) A functional network of intramolecular cross-reacting epitopes delays the elicitation of neutralizing antibodies to Trypanosoma cruzi trans-sialidase. J Infect Dis 3:397–404

    Article  Google Scholar 

  • Pontes de Carvalho LC, Tomlinson S, Nussenzweig V (1993) Trypanosoma rangeli sialidase lacks trans-sialidase activity. Mol Biochem Parasitol 62:19–26

    Article  PubMed  CAS  Google Scholar 

  • Roggentin P, Schauer R, Hoyer LL et al (1993) The sialidase superfamily and its spread by horizontal gene transfer. Mol Microbiol 9:915–921

    Article  PubMed  CAS  Google Scholar 

  • Rubin-de-Celis SS, Uemura H, Yoshida N et al (2006) Expression of trypomastigote trans-sialidase in metacyclic forms of Trypanosoma cruzi increases parasite escape from its parasitophorous vacuole. Cell Microbiol 12:1888–1898

    Google Scholar 

  • Schenkman S, Pontes de Carvalho L, Nussenzweig V (1992) Trypanosoma cruzi trans-sialidase and neuraminidase activities can be mediated by the same enzymes. J Exp Med 175:567–575

    Article  PubMed  CAS  Google Scholar 

  • Schenkman S, Ferguson MAJ, Heise N et al (1993) Mucin-like glycoproteins linked to the membrane by glycosylphosphatidylinositol anchor are the major acceptors of sialic acid in a reaction catalyzed by trans-sialidase in metacyclic forms of Trypanosoma cruzi. Mol Biochem Parasitol 59:293–304

    Article  PubMed  CAS  Google Scholar 

  • Schenkman S, Chaves LB, Pontes de Carvalho L et al (1994a) A proteolytic fragment of Trypanosoma cruzi trans-sialidase lacking the carboxy-terminal domain is active, monomeric and generates antibodies that inhibit enzymatic activity. J Biol Chem 11:7970–7975

    Google Scholar 

  • Schenkman S, Eichinger D, Pereira MEA et al (1994b) Structural and functional properties of Trypanosoma cruzi trans-sialidase. Annu Rev Microbiol 1:499–523

    Article  Google Scholar 

  • Tiralongo E, Martensen I, Grotzinger J et al (2003) Trans-sialidase-like sequences from Trypanosoma congolense conserve most of the critical active site residues found in other trans-sialidases. Biol Chem 8:1203–1213

    Google Scholar 

  • Todeschini AR, Dias WB, Girard MF et al (2004) Enzymatically inactive trans-sialidase from Trypanosoma cruzi binds sialyl and beta-galactopyranosyl residues in a sequential ordered mechanism. J Biol Chem 7:5323–5328

    Google Scholar 

  • Varki A (1997) Sialic acids as ligands in recognition phenomena. FASEB J 4:248–255

    Google Scholar 

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Acknowledgments

 The author would like to thank to Dr. Ricardo Amils Pibernat for reading the manuscript, Veronica Arauco for her helpful edition with Fig. 9.3, Tereza and Silvana Rubin, Omar Cornejo, Lea Bertrand and Chiara Destino as well as the reviewers for their helpful suggestions. The Minister of Science and Technology of Plurinational State of Bolivia financially supported the study. Science Without Borders Program by Conselho Nacional de Desenvolvimento e Tecnologia (CNPq) from Brazil and Erasmus Mundus Program from Europe Union grant the author.

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Authors and Affiliations

  1. Laboratorium voor Microbiële Ecologie en Technologie, Faculteit Bio-ingenieurswetenschappen, Universiteit Gent, Coupure Links 653, B-9000, Gent, Belgium

    Sergio Steven Cornejo Rubin De Celis

  2. Centro Nacional de Investigaciones Biotecnológicas – CNIB, Calle Alcides Arguedas 429, Cala Cala, Cochabamba, Bolívia

    Sergio Steven Cornejo Rubin De Celis

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  1. Sergio Steven Cornejo Rubin De Celis
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Correspondence to Sergio Steven Cornejo Rubin De Celis .

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Editors and Affiliations

  1. Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil

    André L.S. Santos

  2. Departamento de Microbiologia Geral, Ins. de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil

    Marta H. Branquinha

  3. Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

    Claudia M. d’Avila-Levy

  4. Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

    Lucimar F. Kneipp

  5. Departamento de Biologia Celular e Molecular, Instituto de Biologia Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil

    Cátia L. Sodré

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De Celis, S.S.C.R. (2014). Surface Topology Evolution of Trypanosoma Trans-Sialidase. In: Santos, A., Branquinha, M., d’Avila-Levy, C., Kneipp, L., Sodré, C. (eds) Proteins and Proteomics of Leishmania and Trypanosoma. Subcellular Biochemistry, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7305-9_9

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