Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis.,Sharma V, Sharma S, Hoener zu Bentrup K, McKinney JD, Russell DG, Jacobs WR Jr, Sacchettini JC Nat Struct Biol. 2000 Aug;7(8):663-8. PMID:10932251[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sharma V, Sharma S, Hoener zu Bentrup K, McKinney JD, Russell DG, Jacobs WR Jr, Sacchettini JC. Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat Struct Biol. 2000 Aug;7(8):663-8. PMID:10932251 doi:10.1038/77964
