Structural insights into broad substrate range of biphenyl dioxygenases & dehydrogenase
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Biphenyl dioxygenase(BphAE) & biphenyl dehydrogenase(BphB) catalyze first two steps of aerobic degradation of biphenyl & various polychlorinated biphenyls,PCBs. These enzymes are of interest for their potential to oxidize toxic pollutants & manufacture of fine chemicals. We have determined the crystal structures of two variants of BphAE from B. xenovorans LB400, viz BphAERR41 & BphAEp4, evolved by site directed mutagenesis. We have compared the structures of wild type BphAELB400 & BphAEp4. Biochemical properties of BphAELB400 variants with single substitutions, T335A or F336M shows that residue 336 contacts biphenyl & influences regiospecificity of the reaction, but do not enhance enzyme's reactivity toward 2,6-dichlorobiphenyl. However, residue 335 does not contact biphenyl but contributes significantly to expand enzyme's substrate range. Crystal structure of variant BphAERR41 explains the transformation of dibenzofuran & 2-chlorodibenzofuran. This study provides structural insight for expanded substrate range of Rieske-type oxygenases through mutations that enhance the plasticity and/or mobility of enzyme segments lining the catalytic site. Enzyme, BphB catalyze 2nd step of PCB degradation pathway. We have determined the crystal structure of apoenzyme, binary complex with NAD+ & ternary complexes with NAD+2,3-dihydroxybiphenyl from P. pnomenusa B356. A crystal structure representing an intermediate state of the enzyme was also obtained where the substrate binding loop was ordered in comparison with apo & binary forms but was displaced significantly w.r.t ternary structure. These structures reveal that the substrate binding loop is highly mobile & changes conformation during ligand binding, starting from a disorganized loop in apo state to a well organized loop in ligand-bound form. Conformational changes are induced during ligand binding; forming a well defined cavity to accommodate wide range of substrates. For the 1st time, a combination of structural, biochemical, & molecular docking studies of BphBB356 elucidate the unique ability of enzyme to transform the cis-dihydrodiols of double meta-, para-, & ortho-substituted chlorobiphenyls.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 it