Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1756-0500-3-196 http://hdl.handle.net/11449/71821 |
Resumo: | Background. About 130 million people are infected with the hepatitis C virus (HCV) worldwide, but effective treatment options are not yet available. One of the most promising targets for antiviral therapy is nonstructural protein 3 (NS3). To identify possible changes in the structure of NS3 associated with virological sustained response or non-response of patients, a model was constructed for each helicase NS3 protein coding sequence. From this, the goal was to verify the interaction between helicases variants and their ligands. Findings. Evidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites. K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor. Conclusions. Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site. © 2010 Rahal et al; licensee BioMed Central Ltd. |
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Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patientsHepatitis C virusHepatitis C virus genotype 3Background. About 130 million people are infected with the hepatitis C virus (HCV) worldwide, but effective treatment options are not yet available. One of the most promising targets for antiviral therapy is nonstructural protein 3 (NS3). To identify possible changes in the structure of NS3 associated with virological sustained response or non-response of patients, a model was constructed for each helicase NS3 protein coding sequence. From this, the goal was to verify the interaction between helicases variants and their ligands. Findings. Evidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites. K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor. Conclusions. Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site. © 2010 Rahal et al; licensee BioMed Central Ltd.São Paulo State University - UNESP Department of Biology, São José do Rio Preto/SP, CEP: 15054-000Faculty of Medicine University of São Paulo - USP Department of Medical Clinic, São Paulo/SP, CEP: 01246-903Butantan Institute Viral Immunology Laboratory, São Paulo/SPFaculty of Medicine University of São Paulo - USP Department of Gastroenterology, São Paulo/SP, CEP: 05503-900Faculty of Medicine of São José Do Rio Preto, São José do Rio Preto, CEP: 15090-000São Paulo State University - UNESP Center of Study of Social Insects/Department of Biology, Rio Claro/SP, CEP: 13506-900São Paulo State University - UNESP Department of Biology, São José do Rio Preto/SP, CEP: 15054-000São Paulo State University - UNESP Center of Study of Social Insects/Department of Biology, Rio Claro/SP, CEP: 13506-900Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Viral Immunology LaboratoryFaculty of Medicine of São José Do Rio PretoProvazzi, Paola J.S. [UNESP]Arcuri, Helen A.De Carvalho-Mello, Isabel Maria V.G.Pinho, Joo Renato R.Nogueira, Maurício L.Palma, Mario Sergio [UNESP]Rahal, Paula [UNESP]2014-05-27T11:24:46Z2014-05-27T11:24:46Z2010-08-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article196-204application/pdfhttp://dx.doi.org/10.1186/1756-0500-3-196BMC Research Notes, v. 3, p. 196-204, 2010.1756-0500http://hdl.handle.net/11449/7182110.1186/1756-0500-3-1962-s2.0-779555745792-s2.0-77955574579.pdf799108236267121229018886245065350000-0001-5693-6148Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBMC Research Notes0,691info:eu-repo/semantics/openAccess2024-01-16T06:32:38Zoai:repositorio.unesp.br:11449/71821Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-05-23T20:54:05.667824Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients |
title |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients |
spellingShingle |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients Provazzi, Paola J.S. [UNESP] Hepatitis C virus Hepatitis C virus genotype 3 |
title_short |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients |
title_full |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients |
title_fullStr |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients |
title_full_unstemmed |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients |
title_sort |
Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients |
author |
Provazzi, Paola J.S. [UNESP] |
author_facet |
Provazzi, Paola J.S. [UNESP] Arcuri, Helen A. De Carvalho-Mello, Isabel Maria V.G. Pinho, Joo Renato R. Nogueira, Maurício L. Palma, Mario Sergio [UNESP] Rahal, Paula [UNESP] |
author_role |
author |
author2 |
Arcuri, Helen A. De Carvalho-Mello, Isabel Maria V.G. Pinho, Joo Renato R. Nogueira, Maurício L. Palma, Mario Sergio [UNESP] Rahal, Paula [UNESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) Viral Immunology Laboratory Faculty of Medicine of São José Do Rio Preto |
dc.contributor.author.fl_str_mv |
Provazzi, Paola J.S. [UNESP] Arcuri, Helen A. De Carvalho-Mello, Isabel Maria V.G. Pinho, Joo Renato R. Nogueira, Maurício L. Palma, Mario Sergio [UNESP] Rahal, Paula [UNESP] |
dc.subject.por.fl_str_mv |
Hepatitis C virus Hepatitis C virus genotype 3 |
topic |
Hepatitis C virus Hepatitis C virus genotype 3 |
description |
Background. About 130 million people are infected with the hepatitis C virus (HCV) worldwide, but effective treatment options are not yet available. One of the most promising targets for antiviral therapy is nonstructural protein 3 (NS3). To identify possible changes in the structure of NS3 associated with virological sustained response or non-response of patients, a model was constructed for each helicase NS3 protein coding sequence. From this, the goal was to verify the interaction between helicases variants and their ligands. Findings. Evidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites. K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor. Conclusions. Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site. © 2010 Rahal et al; licensee BioMed Central Ltd. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-08-19 2014-05-27T11:24:46Z 2014-05-27T11:24:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1756-0500-3-196 BMC Research Notes, v. 3, p. 196-204, 2010. 1756-0500 http://hdl.handle.net/11449/71821 10.1186/1756-0500-3-196 2-s2.0-77955574579 2-s2.0-77955574579.pdf 7991082362671212 2901888624506535 0000-0001-5693-6148 |
url |
http://dx.doi.org/10.1186/1756-0500-3-196 http://hdl.handle.net/11449/71821 |
identifier_str_mv |
BMC Research Notes, v. 3, p. 196-204, 2010. 1756-0500 10.1186/1756-0500-3-196 2-s2.0-77955574579 2-s2.0-77955574579.pdf 7991082362671212 2901888624506535 0000-0001-5693-6148 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
BMC Research Notes 0,691 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
196-204 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1803045703225704448 |