Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/3847 |
Resumo: | Human immunodeficiency virus (HIV) infections continue to exert an enormous impact on global human health. This led experts to emphasize the importance of new measures for preventing HIV infections, including the development of vaccines and novel drugs. In this context, a promising approach involves the use of lectins that can bind the surface envelope glycoprotein gp120 of HIV with high affinity, preventing viral entry. The cyanobacterial lectin microvirin (MVN) has been proposed as a candidate for development as a topical microbicide because of its ability to bind to high mannose-type glycans, potently inhibiting HIV-1 entry. Thus, the aim of this computational study was to investigate the effects of four point mutations (D53Q, D53E, D53K, and D53W) on the structure and affinity of MVN with di-mannose (MAN). Molecular dynamics simulations followed by binding free energy calculations using MM-GBSA were employed. The calculated binding free energy of ligand-receptor complexation of MVN with MAN was −26.02 kcal mol-1. We identified in the wild-type protein that residues I45, T59, and Q81 have a major contribution to the binding free energy of di-mannose. Among the investigated mutants, the most promising one was the D53W mutation, with a theoretical binding free energy value of −29.16 kcal mol-1. We suggest that this increased stability is due to the introduction of extra rigidity on the hinge region connecting two key structural elements of the MVN binding site. |
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Souza, Rafael Conceição deMuniz, Gabriela de MedeirosSiqueira, Andrei santosLima, Adonis de MeloSilva, Alessandra Pereira daGonçalves, Evonnildo CostaVianez Júnior, João Lídio da Silva Gonçalves2019-08-16T17:00:21Z2019-08-16T17:00:21Z2016SOUZA, Rafael Conceição de et al. Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein. Journal of Molecular Modeling, v. 22, n. 11, p. 269, Nov. 2016.0948-5023https://patua.iec.gov.br/handle/iec/3847Human immunodeficiency virus (HIV) infections continue to exert an enormous impact on global human health. This led experts to emphasize the importance of new measures for preventing HIV infections, including the development of vaccines and novel drugs. In this context, a promising approach involves the use of lectins that can bind the surface envelope glycoprotein gp120 of HIV with high affinity, preventing viral entry. The cyanobacterial lectin microvirin (MVN) has been proposed as a candidate for development as a topical microbicide because of its ability to bind to high mannose-type glycans, potently inhibiting HIV-1 entry. Thus, the aim of this computational study was to investigate the effects of four point mutations (D53Q, D53E, D53K, and D53W) on the structure and affinity of MVN with di-mannose (MAN). Molecular dynamics simulations followed by binding free energy calculations using MM-GBSA were employed. The calculated binding free energy of ligand-receptor complexation of MVN with MAN was −26.02 kcal mol-1. We identified in the wild-type protein that residues I45, T59, and Q81 have a major contribution to the binding free energy of di-mannose. Among the investigated mutants, the most promising one was the D53W mutation, with a theoretical binding free energy value of −29.16 kcal mol-1. We suggest that this increased stability is due to the introduction of extra rigidity on the hinge region connecting two key structural elements of the MVN binding site.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Faculdade Integrada Brasil Amazônia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Faculdade Integrada Brasil Amazônia. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.engSpringer VerlagInvestigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoproteininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleHIVInfecções por HIVinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALInvestigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein.pdfInvestigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein.pdfapplication/pdf551083https://patua.iec.gov.br/bitstreams/92aa18df-4e5d-4018-8ddd-7ba7329884fc/downloadc9a9c128e29cac82a5d7fdf3f4e6da73MD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein |
title |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein |
spellingShingle |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein Souza, Rafael Conceição de HIV Infecções por HIV |
title_short |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein |
title_full |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein |
title_fullStr |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein |
title_full_unstemmed |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein |
title_sort |
Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein |
author |
Souza, Rafael Conceição de |
author_facet |
Souza, Rafael Conceição de Muniz, Gabriela de Medeiros Siqueira, Andrei santos Lima, Adonis de Melo Silva, Alessandra Pereira da Gonçalves, Evonnildo Costa Vianez Júnior, João Lídio da Silva Gonçalves |
author_role |
author |
author2 |
Muniz, Gabriela de Medeiros Siqueira, Andrei santos Lima, Adonis de Melo Silva, Alessandra Pereira da Gonçalves, Evonnildo Costa Vianez Júnior, João Lídio da Silva Gonçalves |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Souza, Rafael Conceição de Muniz, Gabriela de Medeiros Siqueira, Andrei santos Lima, Adonis de Melo Silva, Alessandra Pereira da Gonçalves, Evonnildo Costa Vianez Júnior, João Lídio da Silva Gonçalves |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
HIV Infecções por HIV |
topic |
HIV Infecções por HIV |
description |
Human immunodeficiency virus (HIV) infections continue to exert an enormous impact on global human health. This led experts to emphasize the importance of new measures for preventing HIV infections, including the development of vaccines and novel drugs. In this context, a promising approach involves the use of lectins that can bind the surface envelope glycoprotein gp120 of HIV with high affinity, preventing viral entry. The cyanobacterial lectin microvirin (MVN) has been proposed as a candidate for development as a topical microbicide because of its ability to bind to high mannose-type glycans, potently inhibiting HIV-1 entry. Thus, the aim of this computational study was to investigate the effects of four point mutations (D53Q, D53E, D53K, and D53W) on the structure and affinity of MVN with di-mannose (MAN). Molecular dynamics simulations followed by binding free energy calculations using MM-GBSA were employed. The calculated binding free energy of ligand-receptor complexation of MVN with MAN was −26.02 kcal mol-1. We identified in the wild-type protein that residues I45, T59, and Q81 have a major contribution to the binding free energy of di-mannose. Among the investigated mutants, the most promising one was the D53W mutation, with a theoretical binding free energy value of −29.16 kcal mol-1. We suggest that this increased stability is due to the introduction of extra rigidity on the hinge region connecting two key structural elements of the MVN binding site. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2019-08-16T17:00:21Z |
dc.date.available.fl_str_mv |
2019-08-16T17:00:21Z |
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.citation.fl_str_mv |
SOUZA, Rafael Conceição de et al. Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein. Journal of Molecular Modeling, v. 22, n. 11, p. 269, Nov. 2016. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/3847 |
dc.identifier.issn.-.fl_str_mv |
0948-5023 |
identifier_str_mv |
SOUZA, Rafael Conceição de et al. Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein. Journal of Molecular Modeling, v. 22, n. 11, p. 269, Nov. 2016. 0948-5023 |
url |
https://patua.iec.gov.br/handle/iec/3847 |
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eng |
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eng |
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info:eu-repo/semantics/embargoedAccess |
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dc.publisher.none.fl_str_mv |
Springer Verlag |
publisher.none.fl_str_mv |
Springer Verlag |
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IEC |
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IEC |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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