Functional Expression of All Human Sulfotransferases in Fission Yeast, Assay Development, and Structural Models for Isoforms SULT4A1 and SULT6B1
Bibliographic record
Abstract
Cytosolic sulfotransferases (SULTs) catalyze phase II (conjugation) reactions of drugs and endogenous compounds. A complete set of recombinant fission yeast strains each expressing one of the 14 human SULTs was generated, including SULT4A1 and SULT6B1. Sulfation of test substrates by whole-cell biotransformation was successfully demonstrated for all enzymes for which substrates were previously known. The results proved that the intracellular production of the cofactor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) necessary for SULT activity in fission yeast is sufficiently high to support metabolite production. A modified variant of sulfotransferase assay was also developed that employs permeabilized fission yeast cells (enzyme bags). Using this approach, SULT4A1-dependent sulfation of 1-naphthol was observed. Additionally, a new and convenient SULT activity assay is presented. It is based on the sulfation of a proluciferin compound, which was catalyzed by SULT1E1, SULT2A1, SULT4A1, and SULT6B1. For the latter two enzymes this study represents the first demonstration of their enzymatic functionality. Furthermore, the first catalytically competent homology models for SULT4A1 and SULT6B1 in complex with PAPS are reported. Through mechanistic molecular modeling driven by substrate docking, we pinned down the increased activity levels of these two isoforms to optimized substrate binding.
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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".