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Record W30886713 · doi:10.1096/fasebj.20.5.lb54-b

Expression and purification of active protein kinase Cd (PKCd) kinase domain from E. coli

2006· article· en· W30886713 on OpenAlexaff
James Lloyd Strand, Laura Lin, Divya Chaudhary, Robert Czerwiński, Désirée H.H. Tsao, Yuanhong Li, Karl Malakian, Scott Wolfrom, Yan Liu, Marshall M. Siegel, Ron Kriz, Mark Stahl, Will Somers

Bibliographic record

VenueThe FASEB Journal · 2006
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Kinase Regulation and GTPase Signaling
Canadian institutionsWomen's Health Research Institute
Fundersnot available
KeywordsProtein kinase CProtein kinase domainKinaseRecombinant DNAEnzymeIsozymeBiochemistryMolecular biologyChemistryCyclin-dependent kinase 9BiologyMitogen-activated protein kinase kinaseGene

Abstract

fetched live from OpenAlex

PKC isozymes can be divided into three subfamilies based on structural and enzymatic differences: conventional, novel and atypical. PKCδ is a member of the subfamily of novel PKC's. In an effort to obtain X‐ray crystal structure of this nPKC family target, we expressed and purified a recombinant PKCδ kinase domain construct in E. coli. Here we show that the recombinant kinase domain has activity, is monomeric by size‐exclusion chromatography (SEC), and can auto‐phosphorylate heterogeneously within the cell during expression. PKCδ kinase domain (317–676) was expressed in BL21 cells with a C‐terminal 6‐His tag, and purified +/− ATP to >95% following a four‐step protocol. The purified product eluted as a single, monomeric peak during SEC. Multiple phosphorylations (avg 5–7) were observed by ESI‐MS for both of the +/− ATP preparations; indicating that all phosporylation events most likely occur during expression. In addition, both +/− ATP preparations displayed substrate inhibition with the PKC‐specific FARK inhibitor peptide, while NMR saturation transfer difference (STD) binding experiments showed that AMP‐PNP binds and competes with bisindolylmaleimide for the same active site of PKCδ (317–676). Although, the construct proved difficult to crystallize, we have successfully produced a method for purification of a PKCδ kinase domain from E. coli suitable for assay development, and selectivity studies with other nPKC family members.

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 score0.006
Threshold uncertainty score0.320

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.009
GPT teacher head0.226
Teacher spread0.217 · 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

Citations0
Published2006
Admission routes1
Has abstractyes

Explore more

Same venueThe FASEB JournalSame topicProtein Kinase Regulation and GTPase SignalingFrench-language works237,207