Molecular models of tryptophan synthase from mycobacterium tuberculosis complexed with inhibitors.
The development of new therapies against infectious diseases is vital in developing countries. Among infectious diseases, tuberculosis is considered the leading cause of death. A target for development of new drugs is the tryptophan pathway. The last enzyme of this pathway, tryptophan synthase (TRPS), is responsible for conversion of the indole 3-glycerol phosphate into indol and the condensation of this molecule with serine-producing tryptophan. The present work describes the molecular models of TRPS from Mycobacterium tuberculosis (MtTRPS) complexed with six inhibitors, the indole 3-propanol phosphate and five arylthioalkyl-phosphonated analogs of substrate of the alpha-subunit. The molecular models of MtTRPS present good stereochemistry, and the binding of the inhibitors is favorable. Thus, the generated models can be used in the design of more specific drugs against tuberculosis and other infectious diseases.
Dias
Marcio Vinicius Bertacine
MV
Programa de Pós-Graduação em Biofísica Molecular, Departamento de Física, UNESP, São José do Rio Preto, Brazil.
Canduri
Fernanda
F
da Silveira
Nelson José Freitas
NJ
Czekster
Clarissa Melo
CM
Basso
Luis Augusto
LA
Palma
Mário Sérgio
MS
Santos
Diógenes Santiago
DS
de Azevedo
Walter Filgueira
WF