Your browser doesn't support javascript.
loading
Studying effects of different protonation states of His11 and His102 in ribose-5-phosphate isomerase of Trypanosoma cruzi: an example of cooperative behavior.
Soares, Rafael F; Antunes, Deborah; Santos, Lucianna H S; Rocha, Gisele Vieira; Bastos, Leonardo Soares; Guimarães, Ana Carolina R; Caffarena, Ernesto R.
Afiliação
  • Soares RF; Grupo de Biofísica Computacional e Modelagem Molecular, Programa de Computação Científica, Fiocruz, Rio de Janeiro, Brasil.
  • Antunes D; Grupo de Biofísica Computacional e Modelagem Molecular, Programa de Computação Científica, Fiocruz, Rio de Janeiro, Brasil.
  • Santos LHS; Laboratório de Modelagem Molecular e Planejamento de Fármacos, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
  • Rocha GV; Grupo de Biofísica Computacional e Modelagem Molecular, Programa de Computação Científica, Fiocruz, Rio de Janeiro, Brasil.
  • Bastos LS; Grupo de Biofísica Computacional e Modelagem Molecular, Programa de Computação Científica, Fiocruz, Rio de Janeiro, Brasil.
  • Guimarães ACR; Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brasil.
  • Caffarena ER; Grupo de Biofísica Computacional e Modelagem Molecular, Programa de Computação Científica, Fiocruz, Rio de Janeiro, Brasil.
J Biomol Struct Dyn ; 38(7): 2047-2056, 2020 Apr.
Article em En | MEDLINE | ID: mdl-31184542
The Trypanosoma cruzi ribose-5-phosphate isomerase B (TcRpiB) is a crucial piece in the pentose phosphate pathway and thus is a potential drug target for treatment of Chagas' disease. TcRpiB residues, such as Cys69, Asp45, Glu149 and Pro47, have confirmed their roles in substrate recognition, catalytic reaction and binding site conformation. However, the joint performance of His11 and His102, in the D-ribose-5-phosphate (R5P) in the catalysis is not well understood. In this work, we probed the influence of different protonation states of His11 and His102 on the behavior of the ligand R5P using molecular dynamics simulations, network analysis and thermodynamic integration. Simulations revealed that a protonated His11 combined with a neutral His102 (His11+‒His102) was able to stabilize the ligand R5P in the binding site. Moreover, calculated relative free energy differences showed that when protonated His11 was coupled to a neutral His102 an exergonic process takes place. On the other hand, neutral His11 combined with a protonated His102 (His11‒His102+), sampled conformations that resembled the catalyzed product D-ribulose-5-phosphate (Ru5P). Network analysis also demonstrated some peculiarities for these systems with some negatively correlated nodes in the binding site for His11‒His102+, and exclusive suboptimal paths for His11+‒His102. Therefore, the combined approach presented in this paper proposes two suitable protonation states for the TcRpiB catalytic mechanism, where an extra proton in either histidines might favor R5P binding or influence isomerization reaction to Ru5P. Our results may guide further in silico drug discovery studies. Communicated by Ramaswamy H. Sarma.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Aldose-Cetose Isomerases Idioma: En Revista: J Biomol Struct Dyn Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Aldose-Cetose Isomerases Idioma: En Revista: J Biomol Struct Dyn Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido