| Title | Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. |
| Publication Type | Journal Article |
| Year of Publication | 2002 |
| Authors | Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C |
| Journal | Science |
| Volume | 295 |
| Issue | 5557 |
| Pagination | 1073-7 |
| Date Published | 2002 Feb 8 |
| ISSN | 1095-9203 |
| Keywords | Acyltransferases, 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. |
| DOI | 10.1126/science.1067798 |
| Alternate Journal | Science |
| PubMed ID | 11799204 |
| Grant List | HL61241 / HL / NHLBI NIH HHS / United States P30 CA08748 / CA / NCI NIH HHS / United States |
Submitted by mam2155 on March 24, 2014 - 4:19pm