Role of the Major Antigen of Mycobacterium tuberculosis in Cell Wall Biogenesis

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Science  30 May 1997:
Vol. 276, Issue 5317, pp. 1420-1422
DOI: 10.1126/science.276.5317.1420

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The dominant exported proteins and protective antigens ofMycobacterium tuberculosis are a triad of related gene products called the antigen 85 (Ag85) complex. Each has also been implicated in disease pathogenesis through its fibronectin-binding capacities. A carboxylesterase domain was found within the amino acid sequences of Ag85A, B, and C, and each protein acted as a mycolyltransferase involved in the final stages of mycobacterial cell wall assembly, as shown by direct enzyme assay and site-directed mutagenesis. Furthermore, the use of an antagonist (6-azido-6-deoxy-α,α′-trehalose) of this activity demonstrates that these proteins are essential and potential targets for new antimycobacterial drugs.

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