PMID- 31184542
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20220531
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 38
IP  - 7
DP  - 2020 Apr
TI  - Studying effects of different protonation states of His11 and His102 in 
      ribose-5-phosphate isomerase of Trypanosoma cruzi: an example of cooperative 
      behavior.
PG  - 2047-2056
LID - 10.1080/07391102.2019.1626769 [doi]
AB  - 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.
FAU - Soares, Rafael F
AU  - Soares RF
AUID- ORCID: 0000-0001-8026-2112
AD  - Grupo de Biofisica Computacional e Modelagem Molecular, Programa de Computacao 
      Cientifica, Fiocruz, Rio de Janeiro, Brasil.
FAU - Antunes, Deborah
AU  - Antunes D
AUID- ORCID: 0000-0002-2927-0800
AD  - Grupo de Biofisica Computacional e Modelagem Molecular, Programa de Computacao 
      Cientifica, Fiocruz, Rio de Janeiro, Brasil.
FAU - Santos, Lucianna H S
AU  - Santos LHS
AUID- ORCID: 0000-0002-6910-0697
AD  - Laboratorio de Modelagem Molecular e Planejamento de Farmacos, Departamento de 
      Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal 
      de Minas Gerais, Belo Horizonte, Brasil.
FAU - Rocha, Gisele Vieira
AU  - Rocha GV
AD  - Grupo de Biofisica Computacional e Modelagem Molecular, Programa de Computacao 
      Cientifica, Fiocruz, Rio de Janeiro, Brasil.
FAU - Bastos, Leonardo Soares
AU  - Bastos LS
AD  - Grupo de Biofisica Computacional e Modelagem Molecular, Programa de Computacao 
      Cientifica, Fiocruz, Rio de Janeiro, Brasil.
FAU - Guimaraes, Ana Carolina R
AU  - Guimaraes ACR
AD  - Laboratorio de Genomica Funcional e Bioinformatica, Instituto Oswaldo Cruz, 
      Fiocruz, Rio de Janeiro, Brasil.
FAU - Caffarena, Ernesto R
AU  - Caffarena ER
AUID- ORCID: 0000-0002-8353-3034
AD  - Grupo de Biofisica Computacional e Modelagem Molecular, Programa de Computacao 
      Cientifica, Fiocruz, Rio de Janeiro, Brasil.
LA  - eng
PT  - Journal Article
DEP - 20190611
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - EC 5.3.1.- (Aldose-Ketose Isomerases)
RN  - EC 5.3.1.6 (ribosephosphate isomerase)
SB  - IM
MH  - Aldose-Ketose Isomerases/*chemistry
MH  - Binding Sites
MH  - *Trypanosoma cruzi/enzymology
OTO - NOTNLM
OT  - Trypanosoma cruzi
OT  - molecular dynamics simulation
OT  - network models
OT  - ribose-5-phosphate isomerase
OT  - thermodynamic integration
EDAT- 2019/06/12 06:00
MHDA- 2021/06/22 06:00
CRDT- 2019/06/12 06:00
PHST- 2019/06/12 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2019/06/12 06:00 [entrez]
AID - 10.1080/07391102.2019.1626769 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2020 Apr;38(7):2047-2056. doi: 
      10.1080/07391102.2019.1626769. Epub 2019 Jun 11.