Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Academic Article uri icon

Overview

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 alpha-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.

publication date

  • January 17, 2002

Research

keywords

  • Acyltransferases
  • Dihydrolipoamide Dehydrogenase
  • Mycobacterium tuberculosis
  • Oxidoreductases
  • Peroxidases
  • Thioctic Acid

Identity

Scopus Document Identifier

  • 0037039818

PubMed ID

  • 11799204

Additional Document Info

volume

  • 295

issue

  • 5557