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Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines

Lookup NU author(s): Professor Del Besra

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Abstract

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 Å, reveals an α/β-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 Å 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.

Publication metadata

Author(s): Running DR, Klabunde T, Besra GS, Vissa VD, Belisle JI, Sacchettini JC

Publication type: Article

Publication status: Published

Journal: Nature Structural Biology

Year: 2000

Volume: 7

Issue: 2

Pages: 141-146

ISSN (print): 1545-9993

ISSN (electronic):

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/72413

DOI: 10.1038/72413

PubMed id: 10655617

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