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Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.

TitleMetabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
Publication TypeJournal Article
Year of Publication2002
AuthorsBryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C
JournalScience
Volume295
Issue5557
Pagination1073-7
Date Published2002 Feb 8
ISSN1095-9203
KeywordsAcyltransferases, Amino Acid Sequence, Antioxidants, Binding Sites, Catalysis, Cloning, Molecular, Crystallization, Crystallography, X-Ray, Dihydrolipoamide Dehydrogenase, Hydrogen Bonding, Hydrogen Peroxide, Models, Molecular, Molecular Sequence Data, Mycobacterium tuberculosis, NAD, Oxidation-Reduction, Oxidoreductases, Peroxidases, Peroxiredoxins, Peroxynitrous Acid, Protein Conformation, Protein Folding, Protein Structure, Quaternary, Thioctic Acid, Thioredoxins
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.

DOI10.1126/science.1067798
Alternate JournalScience
PubMed ID11799204
Grant ListHL61241 / HL / NHLBI NIH HHS / United States
P30 CA08748 / CA / NCI NIH HHS / United States

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