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Record W2077939252 · doi:10.1021/ja993805j

Nanomolar versus Millimolar Inhibition by Xylobiose-Derived Azasugars:  Significant Differences between Two Structurally Distinct Xylanases

2000· article· en· W2077939252 on OpenAlexaff
Spencer J. Williams, Roland Hoos, Stephen G. Withers

Bibliographic record

VenueJournal of the American Chemical Society · 2000
Typearticle
Languageen
FieldChemistry
TopicCarbohydrate Chemistry and Synthesis
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsChemistryXylanaseXylobioseStereochemistrySteric effectsResidue (chemistry)Active siteEnzymeGlucosidasesBacillus circulansImidazoleLactamOximeBiochemistry

Abstract

fetched live from OpenAlex

The synthesis of xylobiose-derived nitrogen-containing inhibitors of xylanase is described starting with accessible precursors through efficient synthetic schemes. Four disaccharides were identified as powerful competitive inhibitors of the retaining family 10 xylanase, Cex, from Cellulomonas fimi, namely imidazole ( K i = 150 nM), lactam oxime ( K i = 370 nM), isofagomine ( K i = 130 nM), and deoxynojirimycin ( K i = 5800 nM) derivatives of xylobiose. By contrast, none of the compounds inhibited the family 11 xylanase, Bcx, from Bacillus circulans, to an appreciable extent. Two possible explanations are provided for the discrimination exhibited by the imidazole and the lactam oxime. One explanation relates to the different active site locations of the acid/base residue in the two enzymes: anti to the C1−O5 bond for the family 10 Cex and syn for the family 11 Bcx. The other explanation concerns proposed differences in the transition state conformation for the two enzymes: half-chair for Cex and boat for Bcx. The reasons for the difference in inhibition values between Cex and Bcx for the isofagomine and deoxynojirimycin derivatives are less clear-cut but may be ascribed to destabilizing steric and electrostatic interactions between the inhibitors and an essential tyrosine residue in the active site of Bcx.

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 categoriesInsufficient payload (model declined to judge)
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 score0.007
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.234
Teacher spread0.220 · 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.

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

Citations52
Published2000
Admission routes1
Has abstractyes

Explore more

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