title: Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione.
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.
authors: Departamento de Farmacia, Facultad de Quimica, P. Universidad Catolica de Chile, Macul-Santiago, Chile.
authors: Carlos F
authors: CF
authors: Lagos
authors: Raul
authors: R
authors: Araya-Secchi
authors: Pablo
authors: P
authors: Thomas
authors: Tomás
authors: T
authors: Pérez-Acle
authors: Ricardo A
authors: RA
authors: Tapia
authors: Cristian O
authors: CO
authors: Salas
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D015195:Drug Design; D005721:Glutamate-Cysteine Ligase / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein; D013816:Thermodynamics; D014344:Trypanocidal Agents / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000737:chemistry* / Q000201:enzymology
chemical_list: D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; D014344:Trypanocidal Agents; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione