Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis | Academic Article individual record
abstract

Isocitrate lyase (ICL) plays a pivotal role in the persistence of Mycobacterium tuberculosis in mice by sustaining intracellular infection in inflammatory macrophages. The enzyme allows net carbon gain by diverting acetyl-CoA from beta-oxidation of fatty acids into the glyoxylate shunt pathway. Given its potential as a drug target against persistent infections, we solved its structure without ligand and in complex with two inhibitors. Covalent modification of an active site residue, Cys 191, by the inhibitor 3-bromopyruvate traps the enzyme in a catalytic conformation with the active site completely inaccessible to solvent. The structure of a C191S mutant of the enzyme with the inhibitor 3-nitropropionate provides further insight into the reaction mechanism.

author list (cited authors)
Sharma, V., Sharma, S., zu Bentrup, K. H., McKinney, J. D., Russell, D. G., Jacobs, W. R., & Sacchettini, J. C.
publication date
2000
keywords
  • Glyoxylates
  • Pyruvates
  • Propionates
  • Amino Acid Substitution
  • Isocitrate Lyase
  • Catalysis
  • Protein Binding
  • Crystallography, X-Ray
  • Ligands
  • Binding Sites
  • Protein Structure, Secondary
  • Animals
  • Solvents
  • Propionic Acids
  • Mycobacterium Tuberculosis
  • Protein Structure, Tertiary
  • Nitro Compounds
  • Cysteine
  • Molecular Sequence Data
  • Mutation
  • Models, Molecular
  • Mice
altmetric score

3.0

citation count

166