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Record W2993915081 · doi:10.1038/s41467-019-13348-2

Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors

2019· article· en· W2993915081 on OpenAlexafffund
Anastasiia Gusach, Aleksandra Luginina, Egor Marin, Rebecca L. Brouillette, Élie Besserer‐Offroy, Jean‐Michel Longpré, Andrii Ishchenko, Petr Popov, Nilkanth Patel, Taku Fujimoto, Toru Maruyama, Benjamin Stauch, Margarita Ergasheva, Daria Romanovskaia, A. Stepko, Kirill Kovalev, M.B. Shevtsov, Valentin Gordeliy, Gye Won Han, Vsevolod Katritch, Valentin Borshchevskiy, Philippe Sarret, Alexey Mishin, Vadim Cherezov

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsUniversité de Sherbrooke
FundersNational Institute of General Medical SciencesRussian Science FoundationCentre National de la Recherche ScientifiqueEuropean Synchrotron Radiation FacilityAgence Nationale de la RechercheUniversité de SherbrookeCanadian Institutes of Health ResearchFrench Infrastructure for Integrated Structural BiologyUniversity of Southern CaliforniaMinistry of Science and Higher Education of the Russian FederationU.S. Department of Health and Human Services
KeywordsLigand (biochemistry)AsthmaReceptorMutagenesisLeukotrieneComputational biologyChemistryBiologyMutationGeneticsGeneImmunology

Abstract

fetched live from OpenAlex

Abstract Cysteinyl leukotriene G protein-coupled receptors CysLT 1 and CysLT 2 regulate pro-inflammatory responses associated with allergic disorders. While selective inhibition of CysLT 1 R has been used for treating asthma and associated diseases for over two decades, CysLT 2 R has recently started to emerge as a potential drug target against atopic asthma, brain injury and central nervous system disorders, as well as several types of cancer. Here, we describe four crystal structures of CysLT 2 R in complex with three dual CysLT 1 R/CysLT 2 R antagonists. The reported structures together with the results of comprehensive mutagenesis and computer modeling studies shed light on molecular determinants of CysLTR ligand selectivity and specific effects of disease-related single nucleotide variants.

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 score0.092
Threshold uncertainty score0.307

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 head0.008
GPT teacher head0.263
Teacher spread0.254 · 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

Citations77
Published2019
Admission routes2
Has abstractyes

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