Download MendeleyStructure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis.
Sharma, V., Sharma, S., Hoener zu Bentrup, K., McKinney, J.D., Russell, D.G., Jacobs Jr., W.R., Sacchettini, J.C.(2000) Nat Struct Biol 7: 663-668
- PubMed: 10932251
- DOI: https://doi.org/10.1038/77964
- Primary Citation of Related Structures:
1F61, 1F8I, 1F8M - PubMed 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.
Organizational Affiliation:
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.
