{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:32:52Z","timestamp":1787592772594,"version":"build-2736575974"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2012,1,5]],"date-time":"2012-01-05T00:00:00Z","timestamp":1325721600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1002474","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T04:02:00Z","timestamp":1325822520000},"page":"e1002474","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["Trypanosoma cruzi trans-Sialidase in Complex with a Neutralizing Antibody: Structure\/Function Studies towards the Rational Design of Inhibitors"],"prefix":"10.1371","volume":"8","author":[{"given":"Alejandro","family":"Buschiazzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Mui\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Larrieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Pitcovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Mucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Campetella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,1,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/S0140-6736(10)60061-X","article-title":"Chagas disease.","volume":"375","author":"A Rassi Jr","year":"2010","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1600-065X.1989.tb00558.x","article-title":"Immunobiology of murine <italic>T. cruzi<\/italic> infection: the predominance of parasite-nonspecific responses and the activation of TCRI T cells.","volume":"112","author":"P Minoprio","year":"1989","journal-title":"Immunol Rev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/infdis\/96.3.199","article-title":"Connective tissue reactions in normal and immunized mice to a reticulotropic strain of <italic>Trypanosoma cruzi<\/italic>.","volume":"96","author":"WH Taliaferro","year":"1955","journal-title":"J Infect Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1371\/journal.ppat.0020062","article-title":"The thymus is a common target organ in infectious diseases.","volume":"2","author":"W Savino","year":"2006","journal-title":"PLoS Pathog"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1128\/IAI.73.1.201-207.2005","article-title":"The <italic>trans<\/italic>-sialidase from <italic>Trypanosoma cruzi<\/italic> induces thrombocytopenia during acute Chagas&apos; disease by reducing the platelet sialic acid contents.","volume":"73","author":"MV Tribulatti","year":"2005","journal-title":"Infect Immun"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0090-1229(88)90016-5","article-title":"Serum neuraminidase activity and hematological alterations in acute human Chagas&apos; disease.","volume":"46","author":"EH de Titto","year":"1988","journal-title":"Clin Immunol Immunopathol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1128\/IAI.61.3.898-902.1993","article-title":"Mammalian cell sialic acid enhances invasion by <italic>Trypanosoma cruzi<\/italic>.","volume":"61","author":"RP Schenkman","year":"1993","journal-title":"Infect Immun"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/0092-8674(91)90008-M","article-title":"A novel cell surface <italic>trans<\/italic>-sialidase of <italic>Trypanosoma cruzi<\/italic> generates a stage-specific epitope required for invasion of mammalian cells.","volume":"65","author":"S Schenkman","year":"1991","journal-title":"Cell"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.4049\/jimmunol.153.7.3141","article-title":"Role of sialic acid in the resistance of <italic>Trypanosoma cruzi<\/italic> trypomastigotes to complement.","volume":"153","author":"S Tomlinson","year":"1994","journal-title":"J Immunol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1242\/jcs.113.7.1299","article-title":"Mucin-like molecules form a negatively charged coat that protects <italic>Trypanosoma cruzi<\/italic> trypomastigotes from killing by human anti-alpha-galactosyl antibodies.","volume":"113","author":"VL Pereira-Chioccola","year":"2000","journal-title":"J Cell Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0166-6851(85)90051-9","article-title":"Incorporation of sialic acid into <italic>Trypanosoma cruzi<\/italic> macromolecules. A proposal for a new metabolic route.","volume":"16","author":"JO Previato","year":"1985","journal-title":"Mol Biochem Parasitol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1111\/j.1462-5822.2006.00755.x","article-title":"Expression of trypomastigote <italic>trans<\/italic>-sialidase in metacyclic forms of <italic>Trypanosoma cruzi<\/italic> increases parasite escape from its parasitophorous vacuole.","volume":"8","author":"SS Rubin-de-Celis","year":"2006","journal-title":"Cell Microbiol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/glycob\/7.6.731","article-title":"The <italic>trans<\/italic>-sialidase of <italic>Trypanosoma cruzi<\/italic> is anchored by two different lipids.","volume":"7","author":"R Agusti","year":"1997","journal-title":"Glycobiology"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1074\/jbc.M311356200","article-title":"Improving protein pharmacokinetics by genetic fusion to simple amino acid sequences.","volume":"279","author":"P Alvarez","year":"2004","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1093\/infdis\/170.6.1570","article-title":"Antibodies inhibiting <italic>Trypanosoma cruzi trans<\/italic>-sialidase activity in sera from human infections.","volume":"170","author":"MS Leguizam\u00f3n","year":"1994","journal-title":"J Infect Dis"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1086\/315001","article-title":"<italic>trans<\/italic>-sialidase from <italic>Trypanosoma cruzi<\/italic> induces apoptosis in cells from the immune system in vivo.","volume":"180","author":"MS Leguizam\u00f3n","year":"1999","journal-title":"J Infect Dis"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1017\/S0031182006001752","article-title":"Immune system pathogenesis is prevented by the neutralization of the systemic <italic>trans<\/italic>-sialidase from <italic>Trypanosoma cruzi<\/italic> during severe infections.","volume":"134","author":"MG Risso","year":"2007","journal-title":"Parasitology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1073\/pnas.052496399","article-title":"Thymocyte depletion in <italic>Trypanosoma cruzi<\/italic> infection is mediated by <italic>trans<\/italic>-sialidase-induced apoptosis on nurse cells complex.","volume":"99","author":"J Mucci","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1084\/jem.181.5.1693","article-title":"<italic>Trypanosoma cruzi trans<\/italic>-sialidase: enhancement of virulence in a murine model of Chagas&apos; disease.","volume":"181","author":"M Chuenkova","year":"1995","journal-title":"J Exp Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1086\/420831","article-title":"Differential expression of a virulence factor, the <italic>trans<\/italic>-sialidase, by the main <italic>Trypanosoma cruzi<\/italic> phylogenetic lineages.","volume":"189","author":"MG Risso","year":"2004","journal-title":"J Infect Dis"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1586\/eri.10.144","article-title":"The urgent need to develop new drugs and tools for the treatment of Chagas disease.","volume":"9","author":"MJ Munoz","year":"2011","journal-title":"Expert Rev Anti Infect Ther"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"5022","DOI":"10.1073\/pnas.0711014105","article-title":"A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes.","volume":"105","author":"SR Wilkinson","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/emboj\/19.1.16","article-title":"Structural basis of sialyltransferase activity in trypanosomal sialidases.","volume":"19","author":"A Buschiazzo","year":"2000","journal-title":"Embo J"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S1097-2765(02)00680-9","article-title":"The crystal structure and mode of action of <italic>trans<\/italic>-sialidase, a key enzyme in <italic>Trypanosoma cruzi<\/italic> pathogenesis.","volume":"10","author":"A Buschiazzo","year":"2002","journal-title":"Mol Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.bmcl.2008.12.065","article-title":"Discovery of novel inhibitors of <italic>Trypanosoma cruzi trans<\/italic>-sialidase from <italic>in silico<\/italic> screening.","volume":"19","author":"J Neres","year":"2009","journal-title":"Bioorg Med Chem Lett"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.drudis.2007.12.004","article-title":"Rational drug design in parasitology: <italic>trans<\/italic>-sialidase as a case study for Chagas disease.","volume":"13","author":"J Neres","year":"2008","journal-title":"Drug Discov Today"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1002\/anie.200705435","article-title":"A new generation of specific <italic>Trypanosoma cruzi trans<\/italic>-sialidase inhibitors.","volume":"47","author":"S Buchini","year":"2008","journal-title":"Angew Chem Int Ed Engl"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1086\/341463","article-title":"A functional network of intramolecular cross-reacting epitopes delays the elicitation of neutralizing antibodies to <italic>Trypanosoma cruzi trans<\/italic>-sialidase.","volume":"186","author":"TA Pitcovsky","year":"2002","journal-title":"J Infect Dis"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1128\/IAI.69.3.1869-1875.2001","article-title":"Epitope mapping of <italic>trans<\/italic>-sialidase from <italic>Trypanosoma cruz<\/italic>i reveals the presence of several cross-reactive determinants.","volume":"69","author":"TA Pitcovsky","year":"2001","journal-title":"Infect Immun"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1086\/593697","article-title":"Long-lasting antibodies detected by a <italic>trans<\/italic>-sialidase inhibition assay of sera from parasite-free, serologically cured chagasic patients.","volume":"175","author":"MS Leguizam\u00f3n","year":"1997","journal-title":"J Infect Dis"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/0169-4758(92)90175-2","article-title":"A superfamily of <italic>Trypanosoma cruzi<\/italic> surface antigens.","volume":"8","author":"O Campetella","year":"1992","journal-title":"Parasitol Today"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/glycob\/9.6.581","article-title":"Enzymically inactive members of the <italic>trans<\/italic>-sialidase family from <italic>Trypanosoma cruzi<\/italic> display beta-galactose binding activity.","volume":"9","author":"ML Cremona","year":"1999","journal-title":"Glycobiology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0378-1119(95)00175-6","article-title":"A single tyrosine differentiates active and inactive <italic>Trypanosoma cruzi trans<\/italic>-sialidases.","volume":"160","author":"ML Cremona","year":"1995","journal-title":"Gene"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"7532","DOI":"10.1021\/ja0344967","article-title":"<italic>Trypanosoma cruzi trans<\/italic>-sialidase operates through a covalent sialyl-enzyme intermediate: tyrosine is the catalytic nucleophile.","volume":"125","author":"AG Watts","year":"2003","journal-title":"J Am Chem Soc"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1086\/514199","article-title":"The repetitive domain of <italic>Trypanosoma cruzi trans<\/italic>-sialidase enhances the immune response against the catalytic domain.","volume":"177","author":"CA Buscaglia","year":"1998","journal-title":"J Infect Dis"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0003-2697(86)90211-3","article-title":"Quantitation of picomole levels of <italic>N<\/italic>-acetyl- and <italic>N<\/italic>-glycolylneuraminic acids by a HPLC-adaptation of the thiobarbituric acid assay.","volume":"157","author":"LD Powell","year":"1986","journal-title":"Anal Biochem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1093\/glycob\/cwq037","article-title":"Identification of glycoproteins targeted by <italic>Trypanosoma cruzi trans<\/italic>-sialidase, a virulence factor that disturbs lymphocyte glycosylation.","volume":"20","author":"RP Mui\u00e1","year":"2010","journal-title":"Glycobiology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1107\/S0907444904016427","article-title":"Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT.","volume":"60","author":"E Blanc","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics.","volume":"60","author":"P Emsley","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref40","article-title":"Refinement with Local Structure Similarity Restraints (LSSR) Enables Exploitation of Information from Related Structures and Facilitates use of NCS.","volume":"TP139","author":"OS Smart","year":"2008","journal-title":"Abstr Annu Meet Am Crystallogr Assoc Abstract"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev.bi.59.070190.002255","article-title":"Antibody-antigen complexes.","volume":"59","author":"DR Davies","year":"1990","journal-title":"Annu Rev Biochem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1006\/jmbi.1993.1648","article-title":"Shape complementarity at protein\/protein interfaces.","volume":"234","author":"MC Lawrence","year":"1993","journal-title":"J Mol Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1111\/j.1462-5822.2006.00689.x","article-title":"The <italic>trans<\/italic>-sialidase from <italic>Trypanosoma cruzi<\/italic> triggers apoptosis by target cell sialylation.","volume":"8","author":"J Mucci","year":"2006","journal-title":"Cell Microbiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/0042-6822(88)90640-X","article-title":"Protection against lethal influenza with neuraminidase.","volume":"164","author":"RG Webster","year":"1988","journal-title":"Virology"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.drudis.2008.04.013","article-title":"DARPins: a new generation of protein therapeutics.","volume":"13","author":"MT Stumpp","year":"2008","journal-title":"Drug Discov Today"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/nbt1142","article-title":"Engineered antibody fragments and the rise of single domains.","volume":"23","author":"P Holliger","year":"2005","journal-title":"Nat Biotechnol"},{"key":"ref47","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-01147-4_15","article-title":"PEGylation of Antibody Fragments to Improve Pharmacodynamics and Pharmacokinetics.","author":"A Natarajan","year":"2010"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.jmb.2005.11.061","article-title":"An epidemiologically significant epitope of a 1998 human influenza virus neuraminidase forms a highly hydrated interface in the NA-antibody complex.","volume":"356","author":"L Venkatramani","year":"2006","journal-title":"J Mol Biol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/0022-2836(92)90687-F","article-title":"Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex.","volume":"227","author":"WR Tulip","year":"1992","journal-title":"J Mol Biol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0022-2836(92)90688-G","article-title":"Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface.","volume":"227","author":"WR Tulip","year":"1992","journal-title":"J Mol Biol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0969-2126(00)00074-5","article-title":"The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody.","volume":"2","author":"RL Malby","year":"1994","journal-title":"Structure"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"12274","DOI":"10.1128\/JVI.76.23.12274-12280.2002","article-title":"Antibody epitopes on the neuraminidase of a recent H3N2 influenza virus (A\/Memphis\/31\/98).","volume":"76","author":"U Gulati","year":"2002","journal-title":"J Virol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0022-2836(02)01306-2","article-title":"The high resolution structures of free and inhibitor-bound <italic>Trypanosoma rangeli<\/italic> sialidase and its comparison with <italic>T. cruzi trans<\/italic>-sialidase.","volume":"325","author":"MF Amaya","year":"2003","journal-title":"J Mol Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1747-0285.2007.00599.x","article-title":"Structure-based drug design and the discovery of aliskiren (Tekturna): perseverance and creativity to overcome a R&amp;D pipeline challenge.","volume":"70","author":"NC Cohen","year":"2007","journal-title":"Chem Biol Drug Des"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1046\/j.1432-1033.2002.02968.x","article-title":"The <italic>trans<\/italic>-sialidase from the african trypanosome <italic>Trypanosoma brucei.<\/italic>","volume":"269","author":"G Montagna","year":"2002","journal-title":"Eur J Biochem"},{"key":"ref56","first-page":"703","article-title":"Medium scale production and purification to homogeneity of a recombinant <italic>trans<\/italic>-sialidase from <italic>Trypanosoma cruzi<\/italic>.","volume":"42","author":"A Buschiazzo","year":"1996","journal-title":"Cell Mol Biol (Noisy-le-grand)"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0264-410X(03)00541-3","article-title":"Use of a purified <italic>Trypanosoma cruzi<\/italic> antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes.","volume":"22","author":"FM Frank","year":"2003","journal-title":"Vaccine"},{"key":"ref58","article-title":"Monoclonal antibodies: principles and practices.","author":"JW Goding","year":"1996"},{"key":"ref59","article-title":"Molecular data processing.","author":"AGW Leslie","year":"1990"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: programs for protein crystallography.","volume":"50","year":"1994","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","article-title":"Phaser crystallographic software.","volume":"40","author":"AJ McCoy","year":"2007","journal-title":"J Appl Crystallogr"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: all-atom structure validation for macromolecular crystallography.","volume":"66","author":"VB Chen","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1002474","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T01:42:01Z","timestamp":1686620521000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1002474"}},"subtitle":[],"editor":[{"given":"John M.","family":"Mansfield","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,1,5]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,1,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1002474","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,5]]}}}