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Metabolic Enzymes of Mycobacteria Linked to Antioxidant Defense by a Thioredoxin-Like Protein

Science  08 Feb 2002:
Vol. 295, Issue 5557, pp. 1073-1077
DOI: 10.1126/science.1067798

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Abstract

Mycobacterium tuberculosis (Mtb) mounts a stubborn defense against oxidative and nitrosative components of the immune response. Dihydrolipoamide dehydrogenase (Lpd) and dihydrolipoamide succinyltransferase (SucB) are components of α-ketoacid dehydrogenase complexes that are central to intermediary metabolism. We find that Lpd and SucB support Mtb's antioxidant defense. The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD. The 2.0 angstrom AhpD crystal structure reveals a thioredoxin-like active site that is responsive to lipoamide. We propose that Lpd, SucB (the only lipoyl protein detected in Mtb), AhpD, and AhpC together constitute a nicotinamide adenine dinucleotide (reduced)–dependent peroxidase and peroxynitrite reductase. AhpD thus represents a class of thioredoxin-like molecules that enables an antioxidant defense.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed at Box 65, Weill Medical College, 1300 York Avenue, New York, NY 10021, USA. E-mail: cnathan{at}med.cornell.edu

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