S-nitroso proteome of Mycobacterium tuberculosis: Enzymes of intermediary metabolism and antioxidant defense Journal Article
| Authors: | Rhee, K. Y.; Erdjument-Bromage, H.; Tempst, P.; Nathan, C. F. |
| Article Title: | S-nitroso proteome of Mycobacterium tuberculosis: Enzymes of intermediary metabolism and antioxidant defense |
| Abstract: | The immune response to Mycobacterium tuberculosis (Mtb) includes expression of nitric oxide (NO) synthase (NOS)2, whose products can kill Mtb in vitro with a molar potency greater than that of many conventional antitubercular agents. However, the targets of reactive nitrogen intermediates (RNIs) in Mtb are unknown. One major action of RNIs is protein S-nitrosylation. Here, we describe, to our knowledge, the first proteomic analysis of S-nitrosylation in a whole organism after treating Mtb with bactericidal concentrations of RNIs. The 29 S-nitroso proteins identified are all enzymes, mostly serving intermediary metabolism, lipid metabolism, and/or antioxidant defense. Many are essential or implicated in virulence, including defense against RNIs. For each of two target enzymes tested, lipoamide dehydrogenase and mycobacterial proteasome ATPase, S-nitrosylation caused enzyme inhibition. Moreover, endogenously biotinylated proteins were driven into mixed disulfide complexes. Targeting of metabolic enzymes and antioxidant defenses by means of protein S-nitrosylation and mixed disulfide bonding may contribute to the antimycobacterial actions of RNIs. |
| Keywords: | nonhuman; proteome; animal cell; mouse; animals; mice; enzyme inhibition; bacterial virulence; bacteria (microorganisms); animalia; mycobacterium tuberculosis; bacterial proteins; enzyme analysis; antioxidants; antioxidant activity; adenosine triphosphatase; mycobacterium; lipid metabolism; disulfide; biotinylation; biotin; nitric oxide; antibacterial activity; lipoamide dehydrogenase; dihydrolipoamide dehydrogenase; bacterial enzyme; reactive nitrogen species; nitrosylation; posibacteria; disulfide bond; mycobacterial proteasome atpase |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 102 |
| Issue: | 2 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2005-01-11 |
| Start Page: | 467 |
| End Page: | 472 |
| Language: | English |
| DOI: | 10.1073/pnas.0406133102 |
| PUBMED: | 15626759 |
| PROVIDER: | scopus |
| PMCID: | PMC544291 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 75" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Source: Scopus" |
