Sad from Proteobacteria is a Structurally Distinct ALDH3 Enzyme Specialized for the Oxidation of Steroidal Aldehydes
Bibliographic record
Abstract
Abstract The steroid aldehyde dehydrogenase (Sad) from Proteobacteria is a class 3 aldehyde dehydrogenase (ALDH3) that catalyzes the oxidation of C3 steroid side chain aldehydes during bile acid catabolism. The 1.8 Å structure of the enzyme revealed an expanded active site that was able to accommodate bulky steroids, including bile acid intermediates and cholesterol derivatives, with minimal selectivity for ring-conformation or hydroxylation. Sad can utilize both NAD+ and NADP+ as coenzymes, likely due to a truncated N-terminus and a flexible Glu149 residue, which can avoid steric and electrostatic repulsion with the 2′-phosphate of NADP+ while retaining the ability to hydrogen bond to the C2′-OH of NAD+. Sad was over 1000-fold more specific for steroid aldehyde substrates than for smaller molecules such as benzaldehyde. Structural comparison with the homologousPseudomonas putida benzaldehyde dehydrogenase (PpBADH) suggested residues that might contribute to the ability of Sad to utilize bulky steroid substrates. Replacement of these residues in an F400A/L125T PpBADH double-variant resulted in a ∼39-fold increase in catalytic efficiency toward steroid aldehyde compared with the wild-type enzyme. This study advances our understanding of the molecular determinants of substrate specificity within the ALDH3 family and lays the groundwork for biocatalytic applications of steroid aldehyde dehydrogenases in the production of steroid pharmaceuticals and the bioremediation of steroidal pollutants.
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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 | 0.000 |
| 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 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".