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Nat Struct Biol. 2000 Aug;7(8):663-8.

Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis.

Author information

1
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.

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.

PMID:
10932251
DOI:
10.1038/77964
[Indexed for MEDLINE]

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