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Record W3206137714 · doi:10.1002/cbic.202100414

Defluorination Capability of <scp>l</scp>‐2‐Haloacid Dehalogenases in the HAD‐Like Hydrolase Superfamily Correlates with Active Site Compactness

2021· article· en· W3206137714 on OpenAlexafffund
Peter W. Y. Chan, Nilmadhab Chakrabarti, Chris Ing, Ondrej Halgas, Terence To, Marielle Aulikki Wälti, Alain‐Pierre Petit, Christopher Tran, Alexei Savchenko, Alexander F. Yakunin, Elizabeth A. Edwards, Régis Pomès, E.F. Pai

Bibliographic record

VenueChemBioChem · 2021
Typearticle
Languageen
FieldEnvironmental Science
TopicPer- and polyfluoroalkyl substances research
Canadian institutionsUniversity of CalgaryEnvironment and Climate Change CanadaProteinQure (Canada)Princess Margaret Cancer CentreZymeworks (Canada)Hospital for Sick ChildrenSickKids FoundationUniversity of TorontoUniversity Health Network
FundersBiological and Environmental ResearchBasic Energy SciencesNatural Sciences and Engineering Research Council of CanadaOffice of ScienceOntario GenomicsCanada Research ChairsNational Institutes of HealthGovernment of CanadaGenome CanadaOntario Genomics InstituteNational Center for Research ResourcesNational Institute of General Medical SciencesBrookhaven National LaboratoryArgonne National LaboratoryU.S. Department of Energy
KeywordsActive siteDehalogenaseChemistryHydrolaseEnzymeHydrolysisBiocatalysisStereochemistryHalogenFluoroacetateCombinatorial chemistryActive centerCatalysisBiochemistryOrganic chemistryReaction mechanism

Abstract

fetched live from OpenAlex

l-2-Haloacid dehalogenases, industrially and environmentally important enzymes that catalyse cleavage of the carbon-halogen bond in S-2-halocarboxylic acids, were known to hydrolyse chlorinated, brominated and iodinated substrates but no activity towards fluorinated compounds had been reported. A screen for novel dehalogenase activities revealed four l-2-haloacid dehalogenases capable of defluorination. We now report crystal structures for two of these enzymes, Bpro0530 and Rha0230, as well as for the related proteins PA0810 and RSc1362, which hydrolyse chloroacetate but not fluoroacetate, all at ∼2.2 Å resolution. Overall structure and active sites of these enzymes are highly similar. In molecular dynamics (MD) calculations, only the defluorinating enzymes sample more compact conformations, which in turn allow more effective interactions with the small fluorine atom. Structural constraints, based on X-ray structures and MD calculations, correctly predict the defluorination activity of the homologous enzyme ST2570.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.214
Threshold uncertainty score0.568

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.014
GPT teacher head0.240
Teacher spread0.226 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations33
Published2021
Admission routes2
Has abstractyes

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