1n1s › Citations

The high resolution structures of free and inhibitor-bound Trypanosoma rangeli sialidase and its comparison with T. cruzi trans-sialidase.

Amaya MF, Buschiazzo A, Nguyen T, Alzari PM
J Mol Biol 325 773-84 (2003)
Related entries: 1n1t, 1n1v, 1n1y

Cited: 39 times
EuropePMC logo PMID: 12507479

Abstract

The structure of the recombinant Trypanosoma rangeli sialidase (TrSA) has been determined at 1.6A resolution, and the structures of its complexes with the transition state analog inhibitor 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid (DANA), Neu-5-Ac-thio-alpha(2,3)-galactoside (NATG) and N-acetylneuraminic acid (NANA) have been determined at 1.64A, 2.1A and 2.85A, respectively. The 3D structure of TrSA is essentially identical to that of the natural enzyme, except for the absence of covalently attached sugar at five distinct N-glycosylation sites. The protein exhibits a topologically rigid active site architecture that is unaffected by ligand binding. The overall binding of DANA to the active site cleft is similar to that observed for other viral and bacterial sialidases, dominated by the interactions of the inhibitor carboxylate with the conserved arginine triad. However, the interactions of the other pyranoside ring substituents (hydroxyl, N-acetyl and glycerol moieties) differ between trypanosomal, bacterial and viral sialidases, providing a structural basis for specific inhibitor design. Sialic acid is found to bind the enzyme with the sugar ring in a distorted (half-chair or boat) conformation and the 2-OH hydroxyl group at hydrogen bonding distance of the carboxylate of Asp60, substantiating a direct catalytic role for this residue. A detailed comparison of TrSA with the closely related structure of T.cruzi trans-sialidase (TcTS) reveals a highly conserved catalytic center, where subtle structural differences account for strikingly different enzymatic activities and inhibition properties. The structure of TrSA in complex with NATG shows the active site cleft occupied by a smaller compound which could be identified as DANA, probably the product of a hydrolytic side reaction. Indeed, TrSA (but not TcTS) was found to cleave O and S-linked sialylated substrates, further stressing the functional differences between trypanosomal sialidases and trans-sialidases.

Reviews - 1n1s mentioned but not cited (1)

  1. Unraveling virus relationships by structure-based phylogenetic classification. Ng WM, Stelfox AJ, Bowden TA. Virus Evol 6 veaa003 (2020)

Articles - 1n1s mentioned but not cited (3)

  1. Modulation of catalytic function by differential plasticity of the active site: case study of Trypanosoma cruzi trans-sialidase and Trypanosoma rangeli sialidase. Demir O, Roitberg AE. Biochemistry 48 3398-3406 (2009)
  2. Rational design of a new Trypanosoma rangeli trans-sialidase for efficient sialylation of glycans. Jers C, Michalak M, Larsen DM, Kepp KP, Li H, Guo Y, Kirpekar F, Meyer AS, Mikkelsen JD. PLoS ONE 9 e83902 (2014)
  3. Cooperativity of catalytic and lectin-like domain of Trypanosoma congolense trans-sialidase modulates its catalytic activity. Waespy M, Gbem TT, Dinesh Kumar N, Solaiyappan Mani S, Rosenau J, Dietz F, Kelm S. PLoS Negl Trop Dis 16 e0009585 (2022)


Reviews citing this publication (5)

  1. Diversity of microbial sialic acid metabolism. Vimr ER, Kalivoda KA, Deszo EL, Steenbergen SM. Microbiol. Mol. Biol. Rev. 68 132-153 (2004)
  2. Trans-sialidase and mucins of Trypanosoma cruzi: an important interplay for the parasite. Giorgi ME, de Lederkremer RM. Carbohydr. Res. 346 1389-1393 (2011)
  3. The chemistry and biology of trypanosomal trans-sialidases: virulence factors in Chagas disease and sleeping sickness. Schauer R, Kamerling JP. Chembiochem 12 2246-2264 (2011)
  4. Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications. Herreros-Cabello A, Callejas-Hernández F, Gironès N, Fresno M. Genes (Basel) 11 E1196 (2020)
  5. Modulation of Cell Sialoglycophenotype: A Stylish Mechanism Adopted by Trypanosoma cruzi to Ensure Its Persistence in the Infected Host. Freire-de-Lima L, da Fonseca LM, da Silva VA, da Costa KM, Morrot A, Freire-de-Lima CG, Previato JO, Mendonça-Previato L. Front Microbiol 7 698 (2016)

Articles citing this publication (30)

  1. Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion. Zaitsev V, von Itzstein M, Groves D, Kiefel M, Takimoto T, Portner A, Taylor G. J. Virol. 78 3733-3741 (2004)
  2. Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog. Chiu CP, Watts AG, Lairson LL, Gilbert M, Lim D, Wakarchuk WW, Withers SG, Strynadka NC. Nat. Struct. Mol. Biol. 11 163-170 (2004)
  3. Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase. Amaya MF, Watts AG, Damager I, Wehenkel A, Nguyen T, Buschiazzo A, Paris G, Frasch AC, Withers SG, Alzari PM. Structure 12 775-784 (2004)
  4. Crystal structure of the NanB sialidase from Streptococcus pneumoniae. Xu G, Potter JA, Russell RJ, Oggioni MR, Andrew PW, Taylor GL. J. Mol. Biol. 384 436-449 (2008)
  5. A sialidase mutant displaying trans-sialidase activity. Paris G, Ratier L, Amaya MF, Nguyen T, Alzari PM, Frasch AC. J. Mol. Biol. 345 923-934 (2005)
  6. Dependence of neurotrophic factor activation of Trk tyrosine kinase receptors on cellular sialidase. Woronowicz A, Amith SR, De Vusser K, Laroy W, Contreras R, Basta S, Szewczuk MR. Glycobiology 17 10-24 (2007)
  7. Glycosynthesis in a waterworld: new insight into the molecular basis of transglycosylation in retaining glycoside hydrolases. Bissaro B, Monsan P, Fauré R, O'Donohue MJ. Biochem. J. 467 17-35 (2015)
  8. Molecular characterisation of Trypanosoma rangeli strains isolated from Rhodnius ecuadoriensis in Peru, R. colombiensis in Colombia and R. pallescens in Panama, supports a co-evolutionary association between parasites and vectors. Urrea DA, Carranza JC, Cuba CA, Gurgel-Gonçalves R, Guhl F, Schofield CJ, Triana O, Vallejo GA. Infect. Genet. Evol. 5 123-129 (2005)
  9. Genome of the avirulent human-infective trypanosome--Trypanosoma rangeli. Stoco PH, Wagner G, Talavera-Lopez C, Gerber A, Zaha A, Thompson CE, Bartholomeu DC, Lückemeyer DD, Bahia D, Loreto E, Prestes EB, Lima FM, Rodrigues-Luiz G, Vallejo GA, Filho JF, Schenkman S, Monteiro KM, Tyler KM, de Almeida LG, Ortiz MF, Chiurillo MA, de Moraes MH, Cunha Ode L, Mendonça-Neto R, Silva R, Teixeira SM, Murta SM, Sincero TC, Mendes TA, Urmenyi TP, Silva VG, DaRocha WD, Andersson B, Romanha AJ, Steindel M, de Vasconcelos AT, Grisard EC. PLoS Negl Trop Dis 8 e3176 (2014)
  10. Trypanosoma cruzi trans-sialidase in complex with a neutralizing antibody: structure/function studies towards the rational design of inhibitors. Buschiazzo A, Muiá R, Larrieux N, Pitcovsky T, Mucci J, Campetella O. PLoS Pathog. 8 e1002474 (2012)
  11. Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase. Neres J, Bonnet P, Edwards PN, Kotian PL, Buschiazzo A, Alzari PM, Bryce RA, Douglas KT. Bioorg. Med. Chem. 15 2106-2119 (2007)
  12. Crystal structures of respiratory pathogen neuraminidases. Hsiao YS, Parker D, Ratner AJ, Prince A, Tong L. Biochem. Biophys. Res. Commun. 380 467-471 (2009)
  13. Insight into substrate recognition and catalysis by the human neuraminidase 3 (NEU3) through molecular modeling and site-directed mutagenesis. Albohy A, Li MD, Zheng RB, Zou C, Cairo CW. Glycobiology 20 1127-1138 (2010)
  14. Relevance of the diversity among members of the Trypanosoma cruzi trans-sialidase family analyzed with camelids single-domain antibodies. Ratier L, Urrutia M, Paris G, Zarebski L, Frasch AC, Goldbaum FA. PLoS ONE 3 e3524 (2008)
  15. Structural basis of the interaction of a Trypanosoma cruzi surface molecule implicated in oral infection with host cells and gastric mucin. Cortez C, Yoshida N, Bahia D, Sobreira TJ. PLoS ONE 7 e42153 (2012)
  16. Increasing the transglycosylation activity of alpha-galactosidase from Bifidobacterium adolescentis DSM 20083 by site-directed mutagenesis. Hinz SW, Doeswijk-Voragen CH, Schipperus R, van den Broek LA, Vincken JP, Voragen AG. Biotechnol. Bioeng. 93 122-131 (2006)
  17. Modeling the Trypanosoma cruzi Tc85-11 protein and mapping the laminin-binding site. Marroquin-Quelopana M, Oyama S, Aguiar Pertinhez T, Spisni A, Aparecida Juliano M, Juliano L, Colli W, Alves MJ. Biochem. Biophys. Res. Commun. 325 612-618 (2004)
  18. Carbohydrate Recognition Specificity of Trans-sialidase Lectin Domain from Trypanosoma congolense. Waespy M, Gbem TT, Elenschneider L, Jeck AP, Day CJ, Hartley-Tassell L, Bovin N, Tiralongo J, Haselhorst T, Kelm S. PLoS Negl Trop Dis 9 e0004120 (2015)
  19. Structural and biochemical characterization of the broad substrate specificity of Bacteroides thetaiotaomicron commensal sialidase. Park KH, Kim MG, Ahn HJ, Lee DH, Kim JH, Kim YW, Woo EJ. Biochim. Biophys. Acta 1834 1510-1519 (2013)
  20. Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase. Giorgi ME, Ratier L, Agusti R, Frasch AC, de Lederkremer RM. Glycoconj. J. 27 549-559 (2010)
  21. Characterisation of CMP-sialic acid transporter substrate recognition. Maggioni A, von Itzstein M, Rodríguez Guzmán IB, Ashikov A, Stephens AS, Haselhorst T, Tiralongo J. Chembiochem 14 1936-1942 (2013)
  22. Design of e-pharmacophore models using compound fragments for the trans-sialidase of Trypanosoma cruzi: screening for novel inhibitor scaffolds. Miller BR, Roitberg AE. J. Mol. Graph. Model. 45 84-97 (2013)
  23. Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase. Cano ME, Agusti R, Cagnoni AJ, Tesoriero MF, Kovensky J, Uhrig ML, de Lederkremer RM. Beilstein J Org Chem 10 3073-3086 (2014)
  24. Free-energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase. Pierdominici-Sottile G, Palma J, Roitberg AE. Proteins 82 424-435 (2014)
  25. Design of Trypanosoma rangeli sialidase mutants with improved trans-sialidase activity. Nyffenegger C, Nordvang RT, Jers C, Meyer AS, Mikkelsen JD. PLoS ONE 12 e0171585 (2017)
  26. Improved bioavailability of inhibitors of Trypanosoma cruzi trans-sialidase: PEGylation of lactose analogs with multiarm polyethyleneglycol. Giorgi ME, Ratier L, Agusti R, Frasch AC, de Lederkremer RM. Glycobiology 22 1363-1373 (2012)
  27. Molecular modeling of T. rangeli, T. brucei gambiense, and T. evansi sialidases in complex with the DANA inhibitor. Lima AH, Souza PR, Alencar N, Lameira J, Govender T, Kruger HG, Maguire GE, Alves CN. Chem Biol Drug Des 80 114-120 (2012)
  28. Ganglioside GM3 Analogues Containing Monofluoromethylene-Linked Sialoside: Synthesis, Stereochemical Effects, Conformational Behavior, and Biological Activities. Hirai G, Kato M, Koshino H, Nishizawa E, Oonuma K, Ota E, Watanabe T, Hashizume D, Tamura Y, Okada M, Miyagi T, Sodeoka M. JACS Au 1 137-146 (2021)
  29. Mass Spectrometry-Based Methods to Determine the Substrate Specificities and Kinetics of N-Linked Glycan Hydrolysis by Endo-β-N-Acetylglucosaminidases. Du JJ, Sastre D, Trastoy B, Roberts B, Deredge D, Klontz EH, Flowers MW, Sultana N, Guerin ME, Sundberg EJ. Methods Mol Biol 2674 147-167 (2023)
  30. Production, purification and crystallization of a trans-sialidase from Trypanosoma vivax. Haynes CL, Ameloot P, Remaut H, Callewaert N, Sterckx YG, Magez S. Acta Crystallogr F Struct Biol Commun 71 577-585 (2015)


Related citations provided by authors (1)

  1. Structural basis of sialyltransferase activity in trypanosomal sialidases. Buschiazzo A, Tavares GA, Campetella O, Spinelli S, Cremona ML, Paris G, Amaya MF, Frasch AC, Alzari PM EMBO J. 19 16-24 (2000)

Quick links