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

Overview

MeSH Major

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

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

  • February 8, 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1067798

PubMed ID

  • 11799204

Additional Document Info

start page

  • 1073

end page

  • 7

volume

  • 295

number

  • 5557