Evidence map›Paper›PMID 32142641›Full record

ArticleStructure (London, England : 1993)2020

XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia.

James Zook, Mrinal Shekhar, Debra Hansen, Chelsie Conrad, Thomas Grant, Chitrak Gupta, Thomas White, Anton Barty, Shibom Basu, Yun Zhao and 19 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 9 institutions in 4 countries.

James ZookCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Mrinal ShekharCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; Center for the Development of TherapeuticsThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Debra HansenCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Chelsie ConradHuntsman Cancer Institute, Salt Lake City, UT 84112, USA.
Thomas GrantHauptman Woodward Institute, Jacobs School of Medicine and Biomedical Science, SUNY, Buffalo, NY 14260, USA.
Chitrak GuptaCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Thomas WhiteDESY, Center for Free Electron Laser Science, Hamburg 22607, Germany.
Anton BartyDESY, Center for Free Electron Laser Science, Hamburg 22607, Germany.
Shibom BasuEuropean Molecular Biology Laboratory, Grenoble, Grenoble Cedex 9 38042, France.
Yun ZhaoDepartment of Physics, Arizona State University, Tempe, AZ 85287, USA.
Nadia ZatsepinCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Andrii IshchenkoDepartment of Chemistry, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
Alex BatyukLinac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
Cornelius GatiDESY, Center for Free Electron Laser Science, Hamburg 22607, Germany.
Chufeng LiDepartment of Physics, Arizona State University, Tempe, AZ 85287, USA.
Lorenzo GalliDESY, Center for Free Electron Laser Science, Hamburg 22607, Germany.
Jesse CoeSchool of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA.
Mark HunterLinac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
Meng LiangLinac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
Uwe WeierstallCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Garret NelsonDepartment of Physics, Arizona State University, Tempe, AZ 85287, USA.
Daniel JamesPaul Scherrer Institute, 5232 Villigen, Switzerland.
Benjamin StauchHuntsman Cancer Institute, Salt Lake City, UT 84112, USA.
Felicia CraciunescuCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Darren ThifaultCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Wei LiuCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA.
Vadim CherezovDepartment of Chemistry, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
Abhishek SingharoyCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA. Electronic address: asinghar@asu.edu.
Petra FrommeCenter for Applied Structural Discovery, the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA. Electronic address: pfromme@asu.edu.
Arizona State University · USUniversität Hamburg · DESLAC National Accelerator Laboratory · USHuntsman Cancer Institute · USUniversity of Southern California · USBroad Institute · USEuropean Molecular Biology Laboratory · FRHauptman-Woodward Medical Research Institute · USPaul Scherrer Institute · CH

Funding

ZWITTERION SURFACTANT DDMAB FOR IMPROV STABIL OF PROTEINP41RR001209 · NCRR · STANFORD UNIVERSITY · PI SCOTT, EMILY E · 1985 to 2011
$38.9M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Center for the Rational Design of Membrane Protein CrystallographyU54GM094599 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI CAFFREY, MARTIN D. · 2010 to 2014
$6.8M
Femtosecond nano-crystallography of membrane proteinsR01GM095583 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI FROMME, PETRA · 2010 to 2023
$4.3M
NCRR NIH HHS P41 RR001209NIGMS NIH HHS P41 GM103393NIGMS NIH HHS R01 GM095583NIGMS NIH HHS U54 GM094599
6 · The paper itself

Abstract

Francisella tularensis is the causative agent for the potentially fatal disease tularemia. The lipoprotein Flpp3 has been identified as a virulence determinant of tularemia with no sequence homology outside the Francisella genus. We report a room temperature structure of Flpp3 determined by serial femtosecond crystallography that exists in a significantly different conformation than previously described by the NMR-determined structure. Furthermore, we investigated the conformational space and energy barriers between these two structures by molecular dynamics umbrella sampling and identified three low-energy intermediate states, transitions between which readily occur at room temperature. We have also begun to investigate organic compounds in silico that may act as inhibitors to Flpp3. This work paves the road to developing targeted therapeutics against tularemia and aides in our understanding of the disease mechanisms of tularemia.

Indexed as

Francisella tularensisAnti-Bacterial AgentsCrystallography, X-RayDatabases, PharmaceuticalDrug Evaluation, PreclinicalHumansHydrophobic and Hydrophilic InteractionsLasersLipoproteinsMolecular Dynamics SimulationMolecular Targeted TherapyNuclear Magnetic Resonance, BiomolecularProtein ConformationTularemiaVirulence FactorsAnti-Bacterial AgentsLipoproteinsVirulence Factorscomputational chemistrydrug discoveryFrancisella tularensisintergrative modelingmolecular biophysicsNMR spectroscopyserial femtosecond crystallographyX-ray crystallography

Identifiers

PMID32142641
PMCPMC9014820
OpenAlexW3009397754

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.