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Characterization of Src kinase kinetic and inhibition mechanisms

2008· article· en· W2998703306 on OpenAlexaff
Brooke M. Swalm, Mehul Patel

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldEngineering
TopicInnovative Microfluidic and Catalytic Techniques Innovation
Canadian institutionsWomen's Health Research Institute
Fundersnot available
KeywordsChemistryProto-oncogene tyrosine-protein kinase SrcKineticsEnzyme kineticsSubstrate (aquarium)Product inhibitionKinaseBiophysicsNon-competitive inhibitionStereochemistryTyrosine kinaseSteady state (chemistry)Kinetic isotope effectEnzymeBiochemistryActive siteSignal transductionBiologyOrganic chemistry

Abstract

fetched live from OpenAlex

Src Kinase catalyzes phosphoryl transfer from ATP to tyrosine residues on proteins. In this study, we have investigated the steady state kinetics of the Src kinase reaction in a microfluidic chip‐based mobility shift assay using the Caliper LabChip 3000 instrument. Saturation kinetics is observed with both ATP and a gastrin‐derived peptide substrate. The bireactant kinetics observed suggest a sequential kinetic mechanism. Comparison of the rates of catalysis in the presence of H 2 O and D 2 O yields a significant solvent kinetic isotope effect on Vmax with a value of 3.3 ± 0.2, but no effect on V/K for either ATP or the peptide substrate. This observation suggests that the isotope sensitive step occurs after the first irreversible step, the release of the first product in the reaction cycle. To further support drug discovery efforts, the mechanism of small molecule inhibitors of Src kinase was determined. Steady state kinetic analysis of the data suggests that all of the compounds are competitive against ATP. The binding of these inhibitors to the ATP site is further supported by double inhibition (Yonetani‐Theorell) analysis, using a known competitive inhibitor of Src kinase.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
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 head0.012
GPT teacher head0.201
Teacher spread0.189 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2008
Admission routes1
Has abstractyes

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