Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Academic Article uri icon


  • 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.

published proceedings

  • Nat Struct Biol

altmetric score

  • 3

author list (cited authors)

  • Sharma, V., Sharma, S., Hoener zu Bentrup, K., McKinney, J. D., Russell, D. G., Jacobs, W. R., & Sacchettini, J. C.

citation count

  • 206

complete list of authors

  • Sharma, V||Sharma, S||Hoener zu Bentrup, K||McKinney, JD||Russell, DG||Jacobs, WR||Sacchettini, JC

publication date

  • August 2000