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Dynamic Conformational Changes of Calmodulin when Bound to Nitric Oxide Synthase using FRET

2008· article· en· W3173398541 on OpenAlexafffund
Donald E. Spratt, Valentina Taiakina, J. Guy Guillemette

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldMedicine
TopicNitric Oxide and Endothelin Effects
Canadian institutionsUniversity of Waterloo
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsCalmodulinFörster resonance energy transferChemistryNitric oxide synthaseCysteineEnzymeBiophysicsCofactorMutagenesisGene isoformNitric oxideConformational changeBiochemistryMutantFluorescenceBiology

Abstract

fetched live from OpenAlex

Calmodulin (CaM) is a ubiquitous Ca2+‐sensor protein that binds and activates the Nitric Oxide Synthase (NOS) enzymes (E.C. ). Although the structure of CaM has been determined when bound to a peptide derived from the CaM‐binding domain of endothelial NOS, the conformation of CaM when bound to the three mammalian NOS holoenzymes has yet to be determined. The objective of this study is to determine the dynamic conformational changes of CaM when bound to all three NOS isoforms through the use of Förster Resonance Energy Transfer (FRET). We have produced a double cysteine CaM mutant (T34C/T110C) using site‐directed mutagenesis for the performance of FRET measurements. Far‐red shifted fluorescent dyes were employed so that they could be selectively excited in the presence of the NOS cofactors that absorb light strongly between 250 and 500 nm. FRET studies were performed in the presence of a range of physiologically relevant free Ca2+ concentrations for CaM binding to the constitutive NOS enzymes. These studies will provide a better understanding of the differences between the Ca2+‐dependent and Ca2+‐independent binding of CaM to the NOS isozymes. This work is supported by NSERC (J.G.G.).

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)0.000
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 score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0010.001
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 head0.033
GPT teacher head0.281
Teacher spread0.248 · 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 routes2
Has abstractyes

Explore more

Same venueThe FASEB Journal→Same topicNitric Oxide and Endothelin Effects→French-language works237,207→