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 β-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.
Original language | English (US) |
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Pages (from-to) | 663-668 |
Number of pages | 6 |
Journal | Nature Structural Biology |
Volume | 7 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2000 |
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Genetics