Artigo

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

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...

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Autor principal: Souza, Rafael Concei??o de
Outros Autores: Muniz, Gabriela de Medeiros, Siqueira, Andrei santos, Lima, Adonis de Melo, Silva, Alessandra Pereira da, Gon?alves, Evonnildo Costa, Vianez J?nior, Jo?o L?dio da Silva Gon?alves
Grau: Artigo
Idioma: eng
Publicado em: Springer Verlag 2019
Assuntos:
HIV
Infec??es por HIV
Acesso em linha: http://patua.iec.gov.br//handle/iec/3847
id ir-iec-3847
recordtype dspace
spelling ir-iec-38472019-08-16T17:05:16Z 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 Concei??o de Muniz, Gabriela de Medeiros Siqueira, Andrei santos Lima, Adonis de Melo Silva, Alessandra Pereira da Gon?alves, Evonnildo Costa Vianez J?nior, Jo?o L?dio da Silva Gon?alves HIV Infec??es por HIV 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. 2019-08-16T17:00:21Z 2019-08-16T17:00:21Z 2016 Artigo SOUZA, Rafael Concei??o 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 http://patua.iec.gov.br//handle/iec/3847 eng Acesso Embargado application/pdf Springer Verlag
institution Instituto Evandro Chagas (IEC)
collection PATUA
language eng
topic HIV
Infec??es por HIV
spellingShingle HIV
Infec??es por HIV
Souza, Rafael Concei??o de
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
topic_facet HIV
Infec??es 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.
format Artigo
author Souza, Rafael Concei??o de
author2 Muniz, Gabriela de Medeiros
Siqueira, Andrei santos
Lima, Adonis de Melo
Silva, Alessandra Pereira da
Gon?alves, Evonnildo Costa
Vianez J?nior, Jo?o L?dio da Silva Gon?alves
author2Str Muniz, Gabriela de Medeiros
Siqueira, Andrei santos
Lima, Adonis de Melo
Silva, Alessandra Pereira da
Gon?alves, Evonnildo Costa
Vianez J?nior, Jo?o L?dio da Silva Gon?alves
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
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
publisher Springer Verlag
publishDate 2019
url http://patua.iec.gov.br//handle/iec/3847
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score 11.753735

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