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Record W2996694517 · doi:10.1101/2019.12.22.885152

Cryo-EM Structures and Regulation of Arabinofuranosyltransferase AftD from Mycobacteria

2019· preprint· en· W2996694517 on OpenAlexafffund
Yong Zi Tan, Lei Zhang, José Rodrigues, Ruixiang Blake Zheng, Sabrina I. Giacometti, Ana Lúcia Rosário, Brian Kloss, Venkata P. Dandey, Hui Wei, Richard Brunton, Ashleigh M. Raczkowski, Diogo Athayde, Maria João Catalão, Madalena Pimentel, Oliver B. Clarke, Todd L. Lowary, Margarida Archer, Michael Niederweis, Clinton S. Potter, Bridget Carragher, Filippo Mancia

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGlycosylation and Glycoproteins Research
Canadian institutionsAlberta Glycomics CentreUniversity of Alberta
FundersFundação para a Ciência e a TecnologiaWeill Cornell Medical CollegeAlberta Glycomics CentreUniversity of Alabama at BirminghamAgency for Science, Technology and ResearchUniversity of AlabamaNational Institutes of HealthIowa State UniversitySimons Foundation
KeywordsLipoarabinomannanMycobacterium smegmatisGlycanMutagenesisCell envelopeBiochemistryArabinogalactanMycobacterium tuberculosisMutantBiologyConformational changeGlycosyltransferaseCell wallTransferaseChemistryEnzymeEscherichia coliTuberculosisGlycoproteinGene

Abstract

fetched live from OpenAlex

SUMMARY Mycobacterium tuberculosis causes tuberculosis, a disease that kills over one million people each year. Its cell envelope is a common antibiotic target and has a unique structure due, in part, to two lipidated polysaccharides – arabinogalactan and lipoarabinomannan. Arabinofuranosyltransferase D (AftD) is an essential enzyme involved in assembling these glycolipids. We present the 2.9 Å resolution structure of M. abscessus AftD determined by single particle cryo-electron microscopy. AftD has a conserved GT-C glycosyltransferase fold and three carbohydrate binding modules. Glycan array analysis shows that AftD binds complex arabinose glycans. Additionally, AftD is non-covalently complexed with an acyl carrier protein (ACP). 3.4 and 3.5 Å structures of a mutant with impaired ACP binding reveal a conformational change that suggests the ACP may regulate AftD function. Using a conditional knock-out constructed in M. smegmatis , mutagenesis experiments confirm the essentiality of the putative active site and the ACP binding for AftD function.

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 score0.002
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 integrity0.0000.001
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 head0.009
GPT teacher head0.223
Teacher spread0.214 · 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
Published2019
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGlycosylation and Glycoproteins Research→French-language works237,207→