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@ARTICLE{Nass:435344,
author = {Nass, Karol and Redecke, Lars and Perbandt, Markus and
Yefanov, O. and Klinge, M. and Koopmann, R. and Stellato, F.
and Gabdulkhakov, A. and Schönherr, R. and Rehders, D. and
Lahey-Rudolph, J. M. and Aquila, A. and Barty, A. and Basu,
Shibom and Doak, R. Bruce and Duden, R. and Frank, Matthias
and Fromme, Raimund and Kassemeyer, S. and Katona, Gergely
and Kirian, Richard and Liu, H. and Majoul, I. and
Martin-Garcia, J. M. and Messerschmidt, M. and Shoeman, R.
L. and Weierstall, U. and Westenhoff, S. and White, Thomas
and Williams, G. J. and Yoon, C. H. and Zatsepin, Nadia and
Fromme, P. and Duszenko, M. and Chapman, H. N. and Betzel,
C.},
title = {{I}n cellulo crystallization of {T}rypanosoma brucei {IMP}
dehydrogenase enables the identification of genuine
co-factors},
journal = {Nature Communications},
volume = {11},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {PUBDB-2020-00621},
pages = {620},
year = {2020},
note = {open access},
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.},
cin = {CFEL-I / FS-CFEL-1 / UNI/CUI / ASU / DOOR ; HAS-User / U
Lübeck},
ddc = {500},
cid = {I:(DE-H253)CFEL-I-20161114 / I:(DE-H253)FS-CFEL-1-20120731
/ $I:(DE-H253)UNI_CUI-20121230$ / I:(DE-H253)ASU-20151130 /
I:(DE-H253)HAS-User-20120731 /
$I:(DE-H253)U_L__beck-20211012$},
pnm = {6215 - Soft Matter, Health and Life Sciences (POF3-621) /
633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633) / DFG project 194651731 - EXC 1074:
Hamburger Zentrum für ultraschnelle Beobachtung (CUI):
Struktur, Dynamik und Kontrolle von Materie auf atomarer
Skala (194651731) / DFG project 390715994 - EXC 2056: CUI:
Advanced Imaging of Matter (390715994)},
pid = {G:(DE-HGF)POF3-6215 / G:(DE-HGF)POF4-633 /
G:(GEPRIS)194651731 / G:(GEPRIS)390715994},
experiment = {EXP:(DE-H253)CFEL-Exp-20150101 /
EXP:(DE-MLZ)External-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32001697},
UT = {WOS:000512495200001},
doi = {10.1038/s41467-020-14484-w},
url = {https://bib-pubdb1.desy.de/record/435344},
}