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Antigen 85B protein is a major secretory and immunodominant protein of Mycobacterium tuberculosis and part of the antigen 85 complex of three closely related mycolyl-transferase enzymes (Ag85A, Ag85B, Ag85C) responsible for transferring mycolic acids to the arabinogalactan layer and for cord factor biosynthesis in the mycobacterial cell wall[1][3][4][5][7][8]. Ag85B is a potent immunogen, central to cellular immune responses to tuberculosis, and considered a highly promising candidate target for tuberculosis vaccine development, as well as a molecular target for new antitubercular drugs[1][3][4][5]. Structure–function studies show a highly conserved α/β hydrolase fold and active site forming an acyl-enzyme intermediate with the mycolic acid substrate[2][3][4]. No drugs directly targeting Ag85B have yet been approved; however, inhibitors such as ebselen that react with catalytic residues demonstrate the potential for drug discovery[3]. Ag85B is also used as a biomarker for infection and to monitor immune responses in TB research[5].
Inhibitors block mycolyl transferase activity, preventing mycolic acid incorporation into mycobacterial cell wall[3][4] - Inhibitor-induced disruption of active site (e.g., covalent modification at C209 in Ag85C)[3] - Potential vaccine antigen/immune modulator (elicits strong Th1-type immune responses)[1][5]
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