Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment

Detalhes bibliográficos
Autor(a) principal: Capriles, Priscila V. S. Z.
Data de Publicação: 2010
Outros Autores: Guimarães, Ana C. R., Otto, Thomas D., Miranda, Antonio B., Dardenne, Laurent E., Degrave, Wim M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/20739
Resumo: Laboratório Nacional de Computação Científica, LNCC/MCT. Grupo de Modelagem Molecular de Sistemas Biológicos. Petrópolis, RJ, Brasil
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spelling Capriles, Priscila V. S. Z.Guimarães, Ana C. R.Otto, Thomas D.Miranda, Antonio B.Dardenne, Laurent E.Degrave, Wim M.2017-08-24T15:46:50Z2017-08-24T15:46:50Z2010CAPRILES, Priscila V. S. Z. et al. Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment. BMC Genomics, v.11, n.610, 10, 2010.1471-2164https://www.arca.fiocruz.br/handle/icict/2073910.1186/1471-2164-11-610engBioMed CentralTrypanosoma cruziDoença de ChagasMedicamentosTratamentoTrypanosoma cruziChagas DiseaseDrugsTreatmentStructural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatmentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLaboratório Nacional de Computação Científica, LNCC/MCT. Grupo de Modelagem Molecular de Sistemas Biológicos. Petrópolis, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ. Brasil / Parasite Genomics. Wellcome Trust Sanger Institute. Wellcome Trust Genome Campus. Cambridge, UK.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Computacional e Sistemas. Rio de Janeiro, RJ. Brasil.Laboratório Nacional de Computação Científica, LNCC/MCT. Grupo de Modelagem Molecular de Sistemas Biológicos. Petrópolis, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ. Brasil.Background: Trypanosoma cruzi is the etiological agent of Chagas’ disease, an endemic infection that causes thousands of deaths every year in Latin America. Therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. Such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3D) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. In order to find these targets we used the workflows MHOLline and AnEnΠ obtaining 3D models from homologous, analogous and specific proteins of Trypanosoma cruzi versus Homo sapiens. Results: We applied genome wide comparative modelling techniques to obtain 3D models for 3,286 predicted proteins of T. cruzi. In combination with comparative genome analysis to Homo sapiens, we were able to identify a subset of 397 enzyme sequences, of which 356 are homologous, 3 analogous and 38 specific to the parasite. Conclusions: In this work, we present a set of 397 enzyme models of T. cruzi that can constitute potential structure-based drug targets to be investigated for the development of new strategies to fight Chagas’ disease. The strategies presented here support the concept of structural analysis in conjunction with protein functional analysis as an interesting computational methodology to detect potential targets for structure-based rational drug design. For example, 2,4-dienoyl-CoA reductase (EC 1.3.1.34) and triacylglycerol lipase (EC 3.1.1.3), classified as analogous proteins in relation to H. sapiens enzymes, were identified as new potential molecular targets.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/20739/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALana_guimaraes_etal_IOC_2010.pdfana_guimaraes_etal_IOC_2010.pdfapplication/pdf3154672https://www.arca.fiocruz.br/bitstream/icict/20739/2/ana_guimaraes_etal_IOC_2010.pdf6e7bbbe2cfad893c6b585d5c0b146e25MD52TEXTana_guimaraes_etal_IOC_2010.pdf.txtana_guimaraes_etal_IOC_2010.pdf.txtExtracted texttext/plain45610https://www.arca.fiocruz.br/bitstream/icict/20739/3/ana_guimaraes_etal_IOC_2010.pdf.txtf7089b7fb20a383407011d0b6755eb4cMD53icict/207392018-08-15 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dc.title.pt_BR.fl_str_mv Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
title Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
spellingShingle Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
Capriles, Priscila V. S. Z.
Trypanosoma cruzi
Doença de Chagas
Medicamentos
Tratamento
Trypanosoma cruzi
Chagas Disease
Drugs
Treatment
title_short Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
title_full Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
title_fullStr Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
title_full_unstemmed Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
title_sort Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment
author Capriles, Priscila V. S. Z.
author_facet Capriles, Priscila V. S. Z.
Guimarães, Ana C. R.
Otto, Thomas D.
Miranda, Antonio B.
Dardenne, Laurent E.
Degrave, Wim M.
author_role author
author2 Guimarães, Ana C. R.
Otto, Thomas D.
Miranda, Antonio B.
Dardenne, Laurent E.
Degrave, Wim M.
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Capriles, Priscila V. S. Z.
Guimarães, Ana C. R.
Otto, Thomas D.
Miranda, Antonio B.
Dardenne, Laurent E.
Degrave, Wim M.
dc.subject.other.pt_BR.fl_str_mv Trypanosoma cruzi
Doença de Chagas
Medicamentos
Tratamento
topic Trypanosoma cruzi
Doença de Chagas
Medicamentos
Tratamento
Trypanosoma cruzi
Chagas Disease
Drugs
Treatment
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Chagas Disease
Drugs
Treatment
description Laboratório Nacional de Computação Científica, LNCC/MCT. Grupo de Modelagem Molecular de Sistemas Biológicos. Petrópolis, RJ, Brasil
publishDate 2010
dc.date.issued.fl_str_mv 2010
dc.date.accessioned.fl_str_mv 2017-08-24T15:46:50Z
dc.date.available.fl_str_mv 2017-08-24T15:46:50Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv CAPRILES, Priscila V. S. Z. et al. Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment. BMC Genomics, v.11, n.610, 10, 2010.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/20739
dc.identifier.issn.pt_BR.fl_str_mv 1471-2164
dc.identifier.doi.none.fl_str_mv 10.1186/1471-2164-11-610
identifier_str_mv CAPRILES, Priscila V. S. Z. et al. Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment. BMC Genomics, v.11, n.610, 10, 2010.
1471-2164
10.1186/1471-2164-11-610
url https://www.arca.fiocruz.br/handle/icict/20739
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
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collection Repositório Institucional da FIOCRUZ (ARCA)
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