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Record W3000496134 · doi:10.1021/acs.biochem.9b00888

Insights into Structural and Dynamical Changes Experienced by Human RNase 6 upon Ligand Binding

2020· article· en· W3000496134 on OpenAlexafffund
Chitra Narayanan, David N. Bernard, Myriam Létourneau, Jacinthe Gagnon, Donald Gagné, Khushboo Bafna, Charles Calmettes, Jean‐François Couture, Pratul K. Agarwal, Nicolas Doucet

Bibliographic record

VenueBiochemistry · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsUniversity of OttawaUniversité LavalPROTEOInstitut National de la Recherche Scientifique
FundersOffice of Advanced CyberinfrastructureFonds de Recherche du Québec - SantéNational Institute of General Medical SciencesNatural Sciences and Engineering Research Council of Canada
KeywordsRNase PRibonucleaseRNase PHPancreatic ribonucleaseLigand (biochemistry)Active siteHydrolaseRNase MRPRNase HEnzymeBinding siteChemistryNucleotideBiologyBiochemistryStereochemistryRNAGene

Abstract

fetched live from OpenAlex

Ribonuclease 6 (RNase 6) is one of eight catalytically active human pancreatic-type RNases that belong to a superfamily of rapidly evolving enzymes. Like some of its human homologues, RNase 6 exhibits host defense properties such as antiviral and antibacterial activities. Recently solved crystal structures of this enzyme in its nucleotide-free form show the conservation of the prototypical kidney-shaped fold preserved among vertebrate RNases, in addition to revealing the presence of a unique secondary active site. In this study, we determine the structural and conformational properties experienced by RNase 6 upon binding to substrate and product analogues. We present the first crystal structures of RNase 6 bound to a nucleotide ligand (adenosine 5′-monophosphate), in addition to RNase 6 bound to phosphate ions. While the enzyme preserves B 2 subsite ligand preferences, our results show a lack of typical B 2 subsite interactions normally observed in homologous ligand-bound RNases. A comparison of the dynamical properties of RNase 6 in its apo-, substrate-, and product-bound states highlight the unique dynamical properties experienced on time scales ranging from nano- to milliseconds. Overall, our results confirm the specific evolutionary adaptation of RNase 6 relative to its unique catalytic and biological activities.

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)0.000
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
Metaresearch0.0000.000
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)0.0010.000

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 head0.010
GPT teacher head0.245
Teacher spread0.235 · 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

Citations10
Published2020
Admission routes2
Has abstractyes

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