Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acyltransferases*
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Amino Acid Sequence
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Antigens, Bacterial / physiology*
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Azides / metabolism
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Bacterial Proteins / physiology
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Cell Wall / metabolism*
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Chromatography, Thin Layer
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Cloning, Molecular
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Cord Factors / antagonists & inhibitors
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Cord Factors / metabolism
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Escherichia coli / drug effects
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Esterification
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Molecular Sequence Data
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / enzymology
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Mycobacterium tuberculosis / immunology
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Mycobacterium tuberculosis / physiology*
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Mycolic Acids / metabolism
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Serine / metabolism
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Trehalose / analogs & derivatives
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Trehalose / metabolism
Substances
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6-azido-6-deoxytrehalose
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Antigens, Bacterial
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Azides
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Bacterial Proteins
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Cord Factors
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Mycolic Acids
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trehalose monomycolate
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Serine
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Trehalose
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Acyltransferases
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antigen 85B, Mycobacterium tuberculosis