Structural characterization of <i>Helicobacter pylori</i> dethiobiotin synthetase reveals differences between family members
Bibliographic record
Abstract
Dethiobiotin synthetase (DTBS) is involved in the biosynthesis of biotin in bacteria, fungi, and plants. As humans lack this pathway, DTBS is a promising antimicrobial drug target. We determined structures of DTBS from Helicobacter pylori (hpDTBS) bound with cofactors and a substrate analog, and described its unique characteristics relative to other DTBS proteins. Comparison with bacterial DTBS orthologs revealed considerable structural differences in nucleotide recognition. The C‐terminal region of DTBS proteins, which contains two nucleotide‐recognition motifs, differs greatly among DTBS proteins from different species. The structure of hpDTBS revealed that this protein is unique and does not contain a C‐terminal region containing one of the motifs. The single nucleotide‐binding motif in hpDTBS is similar to its counterpart in GTPases; however, isothermal titration calorimetry binding studies showed that hpDTBS has a strong preference for ATP. The structural determinants of ATP specificity were assessed with X‐ray crystallographic studies of hpDTBS·ATP and hpDTBS·GTP complexes. The unique mode of nucleotide recognition in hpDTBS makes this protein a good target for H. pylori ‐specific inhibitors of the biotin synthesis pathway. Database Coordinates and structure factors for structures presented in this article have been deposited in the Protein Data Bank under the following accession codes: 2QMO – apo‐form; 3MLE – hpDTBS·8‐ac·ADP· in P 2 1 2 1 2 1 form; 3QXC – hpDTBS·ATP; 3QXH – hpDTBS·8‐ac:ADP· in C 2 form; 3QXJ – hpDTBS·GTP; 3QXS – hpDTBS·ANP; 3QXX – 8‐ac·GDP· ; and 3QY0 – hpDTBS·GDP· . Structured digital abstract hpDTBS and hpDTBS bind by x‐ray crystallography ( View interaction )
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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) | 0.000 | 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".