Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines
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The antigen 85 (ag85) complex, composed of three proteins (ag85A, B and C), is a major protein component of the Mycobacterium tuberculosis cell wall. Each protein possesses a mycolyltransferase activity required for the biogenesis of trehalose dimycolate (cord factor), a dominant structure necessary for maintaining cell wall integrity. The crystal structure of recombinant ag85C from M. tuberculosis, refined to a resolution of 1.5 A, reveals an alpha/beta-hydrolase polypeptide fold, and a catalytic triad formed by Ser 124, Glu 228 and His 260. ag85C complexed with a covalent inhibitor implicates residues Leu 40 and Met 125 as components of the oxyanion hole. A hydrophobic pocket and tunnel extending 21 A into the core of the protein indicates the location of a probable trehalose monomycolate binding site. Also, a large region of conserved surface residues among ag85A, B and C is a probable site for the interaction of ag85 proteins with human fibronectin.
author list (cited authors)
Ronning, D. R., Klabunde, T., Besra, G. S., Vissa, V. D., Belisle, J. T., & Sacchettini, J. C.
complete list of authors
Ronning, DR||Klabunde, T||Besra, GS||Vissa, VD||Belisle, JT||Sacchettini, JC