Crystal structure of the full-length sorbitol operon regulator SorC from<i>Klebsiella pneumoniae</i>: structural evidence for a novel transcriptional regulation mechanism
Bibliographic record
Abstract
Parasitic nematodes cause serious diseases in humans and animals, economically impacting agricultural industries. Chemoprophylaxis offers short-term benefits, but due to rapid development of drug resistance in parasites there is a pressing need for novel treatments of nematode infections. Lipid binding proteins (LBPs) play an important role in parasitic nematode's limited lipid metabolism. Several structurally novel families of LBPs in nematodes have been described, including the fatty acid and retinoid binding protein family (FAR). In C. elegans, used as a model for studying parasitic nematodes, eight Ce-FAR proteins have been described. Here we report the first high resolution structure of a FAR protein -the 1.8 crystal structure of Ce-FAR-7. Ce-FAR-7 has nine helices, packed into a novel fold containing two hydrophobic binding pockets. Pocket P1 can accommodate fatty acids with different length of the aliphatic chain, whereas P2 is more suitable for bulkier ligands like retinoids and other signaling lipids. Our results suggest that retinol binding can be upregulated by casein kinase 2, via phosphorylation of Thr26 positioned at the bottom of the pocket P2. GFP localization in vivo shows, that Ce-FAR-7 is intracellular and present in all development stages of the nematode. It is mainly localized in the excretory cell and head hypodermis region of the worm. However, during starvation its localization changes and Ce-FAR-7 is expressed in the body hypodermis. In conclusion, our study provides the basic structural and functional information for investigation of inhibitors of lipid binding by FAR proteins, which could result in new generation of anti-nematode drugs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".