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Belisle, JT, Vissa, VD, Sievert, T, Takayama, K, Brennan, PJ and Besra, GS (1997) Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276:1420-2


The dominant exported proteins and protective antigens of Mycobacterium 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-alpha, alpha'-trehalose) of this activity demonstrates that these proteins are essential and potential targets for new antimycobacterial drugs.




Acyltransferases; Amino Acid Sequence; Antigens, Bacterial/physiology; Azides/metabolism; Bacterial Proteins/physiology; Cell Wall/metabolism; Chromatography, Thin Layer; Cloning, Molecular; Cord Factors/antagonists & inhibitors; Cord Factors/metabolism; Escherichia coli/drug effects; Esterification; Molecular Sequence Data; Mycobacterium tuberculosis/drug effects; Mycobacterium tuberculosis/enzymology; Mycobacterium tuberculosis/immunology; Mycobacterium tuberculosis/physiology; Mycolic Acids/metabolism; Serine/metabolism; Trehalose/analogs & derivatives; Trehalose/metabolism