Structural and functional features of enzymes of Mycobacterium tuberculosis peptidoglycan biosynthesis as targets for drug development

Gleiciane Leal Moraes, Guelber Cardoso Gomes, Paulo Robson Monteiro De Sousa, Cláudio Nahum Alves, Thavendran Govender, Hendrik G. Kruger, Glenn E.M. Maguire, Gyanu Lamichhane, Jerônimo Lameira

Research output: Contribution to journalReview articlepeer-review

Abstract

Tuberculosis (TB) is the second leading cause of human mortality from infectious diseases worldwide. The WHO reported 1.3 million deaths and 8.6 million new cases of TB in 2012. Mycobacterium tuberculosis (M. tuberculosis), the infectious bacteria that causes TB, is encapsulated by a thick and robust cell wall. The innermost segment of the cell wall is comprised of peptidoglycan, a layer that is required for survival and growth of the pathogen. Enzymes that catalyse biosynthesis of the peptidoglycan are essential and are therefore attractive targets for discovery of novel antibiotics as humans lack similar enzymes making it possible to selectively target bacteria only. In this paper, we have reviewed the structures and functions of enzymes GlmS, GlmM, GlmU, MurA, MurB, MurC, MurD, MurE and MurF from M. tuberculosis that are involved in peptidoglycan biosynthesis. In addition, we report homology modelled 3D structures of those key enzymes from M. tuberculosis of which the structures are still unknown. We demonstrated that natural substrates can be successfully docked into the active sites of the GlmS and GlmU respectively. It is therefore expected that the models and the data provided herein will facilitate translational research to develop new drugs to treat TB.

Original languageEnglish (US)
Pages (from-to)95-111
Number of pages17
JournalTuberculosis
Volume95
Issue number2
DOIs
StatePublished - Mar 1 2015

Keywords

  • Drug design
  • Homology modelling
  • Peptidoglycan
  • TB

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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