HutZ from <i>Aliivibrio fischeri</i> Inhibits HutW-Mediated Anaerobilin Formation by Sequestering Heme
Bibliographic record
Abstract
Anaerobilin synthase catalyzes the decyclization of the heme protoporphyrin ring, an O 2 -independent reaction that liberates iron and produces the linear tetrapyrrole, anaerobilin. The marine bacterium Aliivibrio fischeri, the enteric pathogen Escherichia coli O157:H7, and the opportunistic oral pathogen Fusobacterium nucleatum encode anaerobilin synthase as part of their heme uptake/utilization operons, designated chu ( E. coli O157:H7), hmu ( F. nucleatum ), and hut ( A. fischeri ). F. nucleatum and E. coli O157:H7 contain accessory proteins (ChuS, ChuY, and HmuF) encoded in their respective operons that mitigate against the cytotoxicity of labile heme and anaerobilin by functioning in heme trafficking and anaerobilin reduction. However, the hut operon of A. fischeri and other members of the Vibrionaceae family including the enteric pathogen Vibrio cholerae do not contain homologues to these accessory proteins, raising questions as to how members of this family mitigate against anaerobilin and heme toxicity. Herein, we show that HutW (anaerobilin synthase) from A. fischeri produces anaerobilin, but that HutX and HutZ, encoded downstream of HutW, do not catalyze anaerobilin reduction in the presence of excess NAD(P)H, FAD, and FMN. However, we show that HutZ prevents labile heme and anaerobilin cytotoxicity by binding tightly to heme, sequestering it from HutW, and preventing anaerobilin formation. Thus, A. fischeri is seemingly unable to extract iron from heme using the hutWXZ gene products. Our results further suggest that the structurally distinct chu, hmu, and hut operons have functionally converged to protect the cell from anaerobilin accumulation and heme cytotoxicity.
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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".