Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione

Lagos, C. F.; Araya-Secchi R.; Thomas P.; Perez-Acle, T; Tapia, R.A.; Salas C.O.

Abstract

Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential drug target to develop novel antichagasic drugs. We have used a variety of computational methods to investigate the interactions between TcGCL with Glutathione (GSH). The three-dimensional structure of TcGCL was constructed by comparative modeling methods using the Saccharomyces cerevisiae glutamate cysteine ligase as template. Molecular dynamics simulations were used to validate the TcGCL model and to analyze the molecular interactions with GSH. Using RMSD clustering, the most prevalent GSH binding modes were identified paying attention to the residues involved in the molecular interactions. The GSH binding modes were used to propose pharmacophore models that can be exploited in further studies to identify novel antichagasic compounds. © Springer-Verlag 2011.

Más información

Título según WOS: Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione
Título según SCOPUS: Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione
Título de la Revista: JOURNAL OF MOLECULAR MODELING
Volumen: 18
Número: 5
Editorial: Springer
Fecha de publicación: 2012
Página de inicio: 2055
Página final: 2064
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-84861231883&partnerID=40&md5=89cfed4b13e4362bcf8db1f1d6716a9a
DOI:

10.1007/s00894-011-1224-z

Notas: ISI, SCOPUS