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, J. M. Lahey-Rudolph, A. Aquila, A. Barty, S. Basu, R. B. Doak, R. Duden, M. Frank, R. Fromme, S. Kassemeyer, G. Katona, R. Kirian, H. Liu, I. Majoul, J. M. Martin-Garcia, M. Messerschmidt, R. L. Shoeman, U. Weierstall, S. Westenhoff, T. A. White, G. J. Williams, C. H. Yoon, N. Zatsepin, P. Fromme, M. Duszenko, H. N. Chapman and C. Betzel ()
Additional contact information
Karol Nass: Deutsches Elektronen-Synchrotron DESY
Lars Redecke: University of Hamburg, and Institute of Biochemistry, University of Lübeck, at Deutsches Elektronen-Synchrotron (DESY)
M. Perbandt: University of Hamburg, at Deutsches Elektronen-Synchrotron (DESY)
O. Yefanov: Deutsches Elektronen-Synchrotron DESY
M. Klinge: University of Hamburg, and Institute of Biochemistry, University of Lübeck, at Deutsches Elektronen-Synchrotron (DESY)
R. Koopmann: University of Tübingen
F. Stellato: Deutsches Elektronen-Synchrotron DESY
A. Gabdulkhakov: Russian Academy of Sciences
R. Schönherr: University of Lübeck
D. Rehders: University of Hamburg, and Institute of Biochemistry, University of Lübeck, at Deutsches Elektronen-Synchrotron (DESY)
J. M. Lahey-Rudolph: Deutsches Elektronen-Synchrotron DESY
A. Aquila: Deutsches Elektronen-Synchrotron DESY
A. Barty: Deutsches Elektronen-Synchrotron DESY
S. Basu: Arizona State University
R. B. Doak: Arizona State University
R. Duden: University of Lübeck
M. Frank: Lawrence Livermore National Laboratory
R. Fromme: Arizona State University
S. Kassemeyer: Max-Planck-Institute for Medical Research
G. Katona: University of Gothenburg
R. Kirian: Arizona State University
H. Liu: Arizona State University
I. Majoul: University of Lübeck
J. M. Martin-Garcia: Arizona State University
M. Messerschmidt: LCLS, SLAC National Accelerator Laboratory
R. L. Shoeman: Max-Planck-Institute for Medical Research
U. Weierstall: Arizona State University
S. Westenhoff: University of Gothenburg
T. A. White: Deutsches Elektronen-Synchrotron DESY
G. J. Williams: LCLS, SLAC National Accelerator Laboratory
C. H. Yoon: Deutsches Elektronen-Synchrotron DESY
N. Zatsepin: Arizona State University
P. Fromme: Arizona State University
M. Duszenko: University of Tübingen
H. N. Chapman: Deutsches Elektronen-Synchrotron DESY
C. Betzel: University of Hamburg, at Deutsches Elektronen-Synchrotron (DESY)

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14484-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14484-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-14484-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().