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

Amino Acid Sequence Animals Binding Sites Catalytic Domain Cloning, Molecular Coenzymes / chemistry Crystallization Guanosine Monophosphate IMP Dehydrogenase / chemistry Models, Molecular Protein Conformation Sf9 Cells Trypanosoma brucei brucei / enzymology

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
30 01 2020
Historique:
received: 31 05 2019
accepted: 06 01 2020
entrez: 1 2 2020
pubmed: 1 2 2020
medline: 24 4 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-14484-w PMID: 32001697 PMC: PMC6992785
pubmed: 32001697
doi: 10.1038/s41467-020-14484-w
pii: 10.1038/s41467-020-14484-w
pmc: PMC6992785
doi:

Substances chimiques

Coenzymes 0
Guanosine Monophosphate 85-32-5
IMP Dehydrogenase EC 1.1.1.205

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

620

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM117342
Pays : United States

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Auteurs

Karol Nass (K)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
Paul Scherrer Institute (PSI), Forschungstrasse 111, 5232, Villigen, PSI, Switzerland.
ORCID: 0000-0001-8843-1566

Lars Redecke (L)

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.
German Centre for Infection Research, University of Lübeck, 23562, Lübeck, Germany.
Institute of Biochemistry, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Deutsches Elektronen Synchrotron (DESY), Photon Science, Notkestr. 85, 22607, Hamburg, Germany.

M Perbandt (M)

Institute of Biochemistry and Molecular Biology, University of Hamburg, at Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, 22607, Hamburg, Germany.
The Hamburg Centre for Ultrafast Imaging (CUI), Luruper Chaussee 149, 22761, Hamburg, Germany.
ORCID: 0000-0001-7517-8522

O Yefanov (O)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.

M Klinge (M)

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.
BioAgilytix Europe GmbH, Lademannbogen 10, 22339, Hamburg, Germany.

R Koopmann (R)

Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str.4, 72076, Tübingen, Germany.
ORCID: 0000-0002-7416-6340

F Stellato (F)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
Dipartimento di Fisica, Università di Roma Tor Vergata and INFN, Via della Ricerca Scientifica 1, 00133, Rome, Italy.

A Gabdulkhakov (A)

Institute of Protein Research, Russian Academy of Sciences, 4 Institutskaya Str., Pushchino, Moscow Region, Russia, 142290.

R Schönherr (R)

Institute of Biochemistry, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Deutsches Elektronen Synchrotron (DESY), Photon Science, Notkestr. 85, 22607, Hamburg, Germany.

D Rehders (D)

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.
BODE Chemie GmbH, Melanchthonstraße 27, 22525, Hamburg, Germany.

J M Lahey-Rudolph (JM)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
Institute of Biochemistry, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
ORCID: 0000-0001-5279-7267

A Aquila (A)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
LCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.

A Barty (A)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.

S Basu (S)

Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.
European Molecular Biology Laboratory (EMBL), Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, Grenoble, France.

R B Doak (RB)

Department of Physics, Arizona State University, Tempe, AZ, 85411, USA.
Max Planck Institute for Medical Research, Jahnstr. 29, 69120, Heidelberg, Germany.

R Duden (R)

Institute of Biology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.

M Frank (M)

Biology and Biotechnology Division, Physical & Life Sciences Directorate, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA, 94550, USA.
ORCID: 0000-0002-5244-0791

R Fromme (R)

Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.
ORCID: 0000-0003-4835-1080

S Kassemeyer (S)

Max-Planck-Institute for Medical Research, Jahnstr. 29, 69120, Heidelberg, Germany.

G Katona (G)

Department of Chemistry and Molecular Biology, University of Gothenburg, 40530, Gothenburg, Sweden.
ORCID: 0000-0002-2031-8716

R Kirian (R)

Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.
ORCID: 0000-0001-7197-3086

H Liu (H)

Department of Physics, Arizona State University, Tempe, AZ, 85411, USA.
Complex Systems Division, Beijing Computational Science Research Center, 100193, Beijing, China.
ORCID: 0000-0001-7324-6632

I Majoul (I)

Institute of Biology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.

J M Martin-Garcia (JM)

Center for Applied Structural Discovery (CASD), Biodesign Institute, Arizona State University, 727 East Tyler Street, Tempe, AZ, 85287, USA.
ORCID: 0000-0002-4558-3858

M Messerschmidt (M)

LCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
Center for Applied Structural Discovery (CASD), Biodesign Institute, Arizona State University, 727 East Tyler Street, Tempe, AZ, 85287, USA.

R L Shoeman (RL)

Max-Planck-Institute for Medical Research, Jahnstr. 29, 69120, Heidelberg, Germany.
ORCID: 0000-0002-1030-6738

U Weierstall (U)

Department of Physics, Arizona State University, Tempe, AZ, 85411, USA.

S Westenhoff (S)

Department of Chemistry and Molecular Biology, University of Gothenburg, 40530, Gothenburg, Sweden.

T A White (TA)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
ORCID: 0000-0002-8407-0270

G J Williams (GJ)

LCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
Brookhaven National Laboratory (BNL), PO Box 5000, Upton, NY, 11973-5000, USA.

C H Yoon (CH)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
LCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.

N Zatsepin (N)

Department of Physics, Arizona State University, Tempe, AZ, 85411, USA.
ARC Centre of Excellence in Advanced Molecular Imaging, Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Victoria, 3086, Australia.
ORCID: 0000-0003-1757-0205

P Fromme (P)

Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287-160, USA.

M Duszenko (M)

Institute of Neurophysiology, University of Tübingen, Keplerstr. 15, 72074, Tübingen, Germany.

H N Chapman (HN)

Center for Free-Electron Laser Science (CFEL), Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607, Hamburg, Germany.
The Hamburg Centre for Ultrafast Imaging (CUI), Luruper Chaussee 149, 22761, Hamburg, Germany.
Department of Physics, University of Hamburg, Luruper Chaussee 149, 22761, Hamburg, Germany.
ORCID: 0000-0002-4655-1743

C Betzel (C)

Institute of Biochemistry and Molecular Biology, University of Hamburg, at Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, 22607, Hamburg, Germany. christian.betzel@uni-hamburg.de.
The Hamburg Centre for Ultrafast Imaging (CUI), Luruper Chaussee 149, 22761, Hamburg, Germany. christian.betzel@uni-hamburg.de.

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Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › In cellulo crystallization of Trypanosoma...
questionsmedicales.fr › Eucaryotes › Animaux › In cellulo crystallization of Trypanosoma...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › In cellulo crystallization of Trypanosoma...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Domaine catalytique › In cellulo crystallization of Trypanosoma...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Clonage moléculaire › In cellulo crystallization of Trypanosoma...
questionsmedicales.fr › Enzymes et coenzymes › Coenzymes › In cellulo crystallization of Trypanosoma...
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