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

Donald R. Running, Thomas Klabunde, Gurdyal S. Besra, Varalakshmi D. Vissa, John I. Belisle, James C. Sacchettini

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)141-146
Number of pages6
JournalNature Structural Biology
Volume7
Issue number2
DOIs
StatePublished - Feb 2000
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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