Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis.
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.
Belisle
J T
JT
Department of Microbiology, Colorado State University, Fort Collins, CO 80523, USA. jbelisle@vines.colostate.edu
Vissa
V D
VD
Sievert
T
T
Takayama
K
K
Brennan
P J
PJ
Besra
G S
GS
D000217:Acyltransferases; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000502:physiology*; D001386:Azides / Q000378:metabolism; D001426:Bacterial Proteins / Q000502:physiology; D002473:Cell Wall / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D003001:Cloning, Molecular; D003311:Cord Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D004951:Esterification; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D009171:Mycolic Acids / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014199:Trehalose / Q000031:analogs & derivatives / Q000378:metabolism
C106082:6-azido-6-deoxytrehalose; D000942:Antigens, Bacterial; D001386:Azides; D001426:Bacterial Proteins; D003311:Cord Factors; D009171:Mycolic Acids; C021099:trehalose monomycolate; D012694:Serine; D014199:Trehalose; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis