Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines | Academic Article individual record
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 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.
publication date
2000
keywords
  • Phosphoric Acid Esters
  • Amino Acid Sequence
  • Fibronectins
  • Catalytic Domain
  • Cell Wall
  • Models, Molecular
  • Antigens, Bacterial
  • Antitubercular Agents
  • Molecular Sequence Data
  • Binding Sites
  • Organophosphates
  • Mycobacterium Tuberculosis
  • Cord Factors
  • Drug Design
  • Recombinant Proteins
  • Protein Conformation
  • Humans
  • Acyltransferases
  • Crystallography, X-Ray
altmetric score

3.0

citation count

145