Co-induction of methyltransferase Rv0560c by naphthoquinones and fibric acids suggests attenuation of isoprenoid quinone action in<i>Mycobacterium tuberculosis</i>
Bibliographic record
Abstract
The superoxide generator menadione was previously demonstrated as an inducer of growth stage dependent protein patterns in Mycobacterium tuberculosis. The present study refines this observation by characterizing a novel 27-kDa protein that had not been observed in previous studies relying on younger cultures. A very similar response, based on two-dimensional gel electrophoretic analyses, was induced by the closely related naphthoquinone plumbagin. The 27-kDa protein was also induced by the pro-oxidant peroxisome proliferator gemfibrozil and to a lesser extent by the structurally related compounds fenofibrate and clofibrate. N-terminal sequence data of proteolytic fragments from the 27-kDa protein demonstrated its identity with protein Rv0560c, previously demonstrated to be inducible by salicylate, which also possesses peroxisome proliferating properties. Protein Rv0560c bears three conserved motifs characteristic of S-adenosylmethionine-dependent methyltransferases. Further sequence similarities suggest a function in the bio syn thesis of isoprenoid compounds, e.g., tocopherol, ubiquinone, and sterols. Such involvement is supported by the recognized yet unexplained widespread interference of menadione, salicylate, and fibrates with the isoprenoid quinones ubiquinone, menaquinone, and vitamin K. Induction of Rv0560c by fibrates, salicylate, and naphthoquinones is thus suggested to be caused by action on the plasma membrane, reminiscent of cytochrome P450BM-3 induction by fibrates in Bacillus megaterium, which catalyzes the hydroxylation of fatty acids and thus modulates membrane properties.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".