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Record W2182832735 · doi:10.1107/s1399004715015497

Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides

2015· article· en· W2182832735 on OpenAlexafffund
Roland Pfoh, E.F. Pai, V. Saridakis

Bibliographic record

VenueActa Crystallographica Section D Biological Crystallography · 2015
Typearticle
Languageen
FieldMedicine
TopicSirtuins and Resveratrol in Medicine
Canadian institutionsPrincess Margaret Cancer CentreCanada Research ChairsUniversity Health NetworkUniversity of New BrunswickUniversity of TorontoYork University
FundersBasic Energy SciencesNational Center for Research ResourcesNational Institute of General Medical SciencesNatural Sciences and Engineering Research Council of CanadaBrookhaven National LaboratoryCanadian Institutes of Health ResearchCanada Research ChairsOffice of ScienceNational Institutes of HealthU.S. Department of Energy
KeywordsNAD+ kinaseNicotinamide mononucleotideActive siteBiochemistryNicotinamideChemistryNucleotideBinding siteStereochemistrySite-directed mutagenesisNicotinamide adenine dinucleotideEnzymeMutant

Abstract

fetched live from OpenAlex

Nicotinamide mononucleotide adenylyltransferase (NMNAT) catalyzes the biosynthesis of NAD(+) and NaAD(+). The crystal structure of NMNAT from Methanobacterium thermoautotrophicum complexed with NAD(+) and SO4(2-) revealed the active-site residues involved in binding and catalysis. Site-directed mutagenesis was used to further characterize the roles played by several of these residues. Arg11 and Arg136 were implicated in binding the phosphate groups of the ATP substrate. Both of these residues were mutated to lysine individually. Arg47 does not interact with either NMN or ATP substrates directly, but was deemed to play a role in binding as it is proximal to Arg11 and Arg136. Arg47 was mutated to lysine and glutamic acid. Surprisingly, when expressed in Escherichia coli all of these NMNAT mutants trapped a molecule of NADP(+) in their active sites. This NADP(+) was bound in a conformation that was quite different from that displayed by NAD(+) in the native enzyme complex. When NADP(+) was co-crystallized with wild-type NMNAT, the same structural arrangement was observed. These studies revealed a different conformation of NADP(+) in the active site of NMNAT, indicating plasticity of the active site.

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 score0.003

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 head0.045
GPT teacher head0.284
Teacher spread0.238 · 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

Citations4
Published2015
Admission routes2
Has abstractyes

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