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Molecular models of tryptophan synthase from Mycobacterium tuberculosis complexed with inhibitors

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Abstract

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-producting 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 α-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.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Biofísica Molecular-Departamento de Física, UNESP, São José do Rio Preto, Brazil

    Marcio Vinicius Bertacine Dias & Nelson José Freitas da Silveira

  2. Departamento de Morfofisiologia-CCBS-UFMS, 79070-900, Campo Grande-MS, Brazil

    Fernanda Canduri

  3. Rede Brasileira de Pesquisas em Tuberculose, Grupo de Microbiologia Molecular e Functional, Centro de Biotecnologia, UFRGS, 91501-970, Porto Alegre-RS, Brazil

    Clarissa Melo Czekster

  4. Faculdade de Biociências-PUCRS, 90619-900, Porto Alegre-RS, Brazil

    Luis Augusto Basso & Walter Filgueira de Azevedo Jr.

  5. Laboratory of Structural Biology and Zoochemistry, CEIS/Department of Biology, Institute of Biosciences, UNESP, 13506-900, Rio Claro, SP, Brazil

    Mário Sérgio Palma

  6. Centro de Pesquisas em Biologia Molecular e Funcional/PUCRS, Avenida Ipiranga, 6681, Tecnopuc, Partenon 90619-900, Porto Alegre, RS, Brazil

    Diógenes Santiago Santos

Authors
  1. Marcio Vinicius Bertacine Dias
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  2. Fernanda Canduri
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  3. Nelson José Freitas da Silveira
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  4. Clarissa Melo Czekster
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  5. Luis Augusto Basso
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  7. Diógenes Santiago Santos
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  8. Walter Filgueira de Azevedo Jr.
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Correspondence to Diógenes Santiago Santos or Walter Filgueira de Azevedo Jr..

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Dias, M.V.B., Canduri, F., da Silveira, N.J.F. et al. Molecular models of tryptophan synthase from Mycobacterium tuberculosis complexed with inhibitors. Cell Biochem Biophys 44, 375–384 (2006). https://doi.org/10.1385/CBB:44:3:375

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  • DOI: https://doi.org/10.1385/CBB:44:3:375

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