Evidence map›Paper›PMID 32001697›Full record

ArticleNature communications2020

In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors.

Karol Nass, Lars Redecke, M Perbandt, O Yefanov, M Klinge, R Koopmann, F Stellato, A Gabdulkhakov, R Schönherr, D Rehders and 26 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 39 citations in OpenAlex.

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  6. A snapshot love story: what serial crystallography has done and will do for us.Acta crystallographica. Section D, Structural biology · 2024
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  9. A journey into the regulatory secrets of theFrontiers in pharmacology · 2024
    Review
  10. Article
  11. The gateway to guanine nucleotides: Allosteric regulation of IMP dehydrogenases.Protein science : a publication of the Protein Society · 2022
    Review
  12. Serial femtosecond crystallography.Nature reviews. Methods primers · 2022
    Article
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  17. Can (We Make)Toxins · 2021
    Review
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  20. Rapid screening ofJournal of applied crystallography · 2020
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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

36 authors at 15 institutions in 9 countries.

Karol Nass *Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.ORCID http://orcid.org/0000-0001-8843-1566
Lars Redecke *Joint Laboratory for Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, and Institute of Biochemistry, University of Lübeck, at Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, 22607, Hamburg, Germany.
M PerbandtInstitute of Biochemistry and Molecular Biology, University of Hamburg, at Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, 22607, Hamburg, Germany.ORCID http://orcid.org/0000-0001-7517-8522
O YefanovCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
M KlingeJoint Laboratory for Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, and Institute of Biochemistry, University of Lübeck, at Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, 22607, Hamburg, Germany.
R KoopmannInterfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str.4, 72076, Tübingen, Germany.ORCID http://orcid.org/0000-0002-7416-6340
F StellatoCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
A GabdulkhakovInstitute of Protein Research, Russian Academy of Sciences, 4 Institutskaya Str., Pushchino, Moscow Region, Russia, 142290.
R SchönherrInstitute of Biochemistry, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
D RehdersJoint Laboratory for Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, and Institute of Biochemistry, University of Lübeck, at Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, 22607, Hamburg, Germany.
J M Lahey-RudolphCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.ORCID http://orcid.org/0000-0001-5279-7267
A AquilaCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
A BartyCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
S BasuDepartment of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.
R B DoakDepartment of Physics, Arizona State University, Tempe, AZ, 85411, USA.
R DudenInstitute of Biology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
M FrankBiology and Biotechnology Division, Physical & Life Sciences Directorate, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA, 94550, USA.ORCID http://orcid.org/0000-0002-5244-0791
R FrommeDepartment of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.ORCID http://orcid.org/0000-0003-4835-1080
S KassemeyerMax-Planck-Institute for Medical Research, Jahnstr. 29, 69120, Heidelberg, Germany.
G KatonaDepartment of Chemistry and Molecular Biology, University of Gothenburg, 40530, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-2031-8716
R KirianDepartment of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.ORCID http://orcid.org/0000-0001-7197-3086
H LiuDepartment of Physics, Arizona State University, Tempe, AZ, 85411, USA.ORCID http://orcid.org/0000-0001-7324-6632
I MajoulInstitute of Biology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
J M Martin-GarciaCenter for Applied Structural Discovery (CASD), Biodesign Institute, Arizona State University, 727 East Tyler Street, Tempe, AZ, 85287, USA.ORCID http://orcid.org/0000-0002-4558-3858
M MesserschmidtLCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
R L ShoemanMax-Planck-Institute for Medical Research, Jahnstr. 29, 69120, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-1030-6738
U WeierstallDepartment of Physics, Arizona State University, Tempe, AZ, 85411, USA.
S WestenhoffDepartment of Chemistry and Molecular Biology, University of Gothenburg, 40530, Gothenburg, Sweden.
T A WhiteCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.ORCID http://orcid.org/0000-0002-8407-0270
G J WilliamsLCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
C H YoonCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
N ZatsepinDepartment of Physics, Arizona State University, Tempe, AZ, 85411, USA.ORCID http://orcid.org/0000-0003-1757-0205
P FrommeDepartment of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.
M DuszenkoInstitute of Neurophysiology, University of Tübingen, Keplerstr. 15, 72074, Tübingen, Germany.
H N ChapmanCenter for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.ORCID http://orcid.org/0000-0002-4655-1743
C BetzelInstitute of Biochemistry and Molecular Biology, University of Hamburg, at Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, 22607, Hamburg, Germany. christian.betzel@uni-hamburg.de.
Universität Hamburg · DEArizona State University · USMax Planck Institute for Medical Research · DEUniversity of Gothenburg · SEUniversity of Lübeck · DEUniversity of Tübingen · DEBeijing Computational Science Research Center · CNBrookhaven National Laboratory · USDeutsches Elektronen-Synchrotron DESY · DEEuropean Molecular Biology Laboratory · FRInstitute of Protein Research · RULa Trobe University · AULawrence Livermore National Laboratory · USSLAC National Accelerator Laboratory · USUniversity of Rome Tor Vergata · IT

Funding

Technology development for biological imaging with x-ray free electron lasersR01GM117342 · NIGMS · LAWRENCE LIVERMORE NATIONAL SECURITY, LLC · PI FRANK, MATTHIAS · 2016 to 2024
$4.8M
NIGMS NIH HHS R01 GM117342
6 · The paper itself

Abstract

Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.

Indexed as

CrystallizationAmino Acid SequenceAnimalsBinding SitesCatalytic DomainCloning, MolecularCoenzymesGuanosine MonophosphateIMP DehydrogenaseModels, MolecularProtein ConformationSf9 CellsTrypanosoma brucei bruceiCoenzymesGuanosine MonophosphateIMP Dehydrogenase

Identifiers

PMID32001697
PMCPMC6992785
OpenAlexW3004080792

What OpenQuestion holds

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Registered trials

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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.