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In cellulo crystall...
In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-01-30
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Springer Science and Business Media LLC,2020
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/291571
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https://gup.ub.gu.se/publication/291571URI
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https://doi.org/10.1038/s41467-020-14484-wDOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 angstrom 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. Trypanosoma brucei inosine-5 '-monophosphate dehydrogenase (IMPDH) is an enzyme in the guanine nucleotide biosynthesis pathway and of interest as a drug target. Here the authors present the 2.8 angstrom room temperature structure of TbIMPDH determined by utilizing X-ray free-electron laser radiation and crystals that were grown in insect cells and find that ATP and GMP are bound at the canonical sites of the Bateman domains.
Subject headings and genre
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NATURVETENSKAP Biologi hsv//swe
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NATURAL SCIENCES Biological Sciences hsv//eng
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inosine 5'-monophosphate dehydrogenase
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serial femtosecond
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crystallography
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vivo protein crystallization
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5-monophosphate
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dehydrogenase
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monophosphate dehydrogenase
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crystal-structure
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radiation-damage
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inhibitors
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mechanism
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reveals
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Science & Technology - Other Topics
Added entries (persons, corporate bodies, meetings, titles ...)
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Redecke, L.
(author)
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Perbandt, M.
(author)
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Yefanov, O.
(author)
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Klinge, M.
(author)
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Koopmann, R.
(author)
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Stellato, F.
(author)
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Gabdulkhakov, A.
(author)
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Schonherr, R.
(author)
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Rehders, D.
(author)
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Lahey-Rudolph, J. M.
(author)
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Aquila, A.
(author)
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Barty, A.
(author)
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Basu, S.
(author)
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Doak, R. B.
(author)
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Duden, R.
(author)
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Frank, M.
(author)
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Fromme, R.
(author)
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Kassemeyer, S.
(author)
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Katona, Gergely,1975Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xkatge
(author)
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Kirian, R.
(author)
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Liu, H.
(author)
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Majoul, I.
(author)
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Martin-Garcia, J. M.
(author)
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Messerschmidt, M.
(author)
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Shoeman, R. L.
(author)
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Weierstall, U.
(author)
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Westenhoff, Sebastian,1978Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xwests
(author)
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White, T. A.
(author)
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Williams, G. J.
(author)
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Yoon, C. H.
(author)
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Zatsepin, N.
(author)
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Fromme, P.
(author)
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Duszenko, M.
(author)
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Chapman, H. N.
(author)
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Betzel, C.
(author)
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Göteborgs universitetInstitutionen för kemi och molekylärbiologi
(creator_code:org_t)
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In:Nature Communications: Springer Science and Business Media LLC11:12041-1723
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Nass, K.
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Redecke, L.
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Perbandt, M.
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Yefanov, O.
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Klinge, M.
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Koopmann, R.
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show more...
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Stellato, F.
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Gabdulkhakov, A.
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Schonherr, R.
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Rehders, D.
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Lahey-Rudolph, J ...
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Aquila, A.
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Barty, A.
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Basu, S.
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Doak, R. B.
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Duden, R.
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Frank, M.
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Fromme, R.
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Kassemeyer, S.
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Katona, Gergely, ...
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Kirian, R.
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Liu, H.
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Majoul, I.
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Martin-Garcia, J ...
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Messerschmidt, M ...
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Shoeman, R. L.
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Weierstall, U.
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Westenhoff, Seba ...
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White, T. A.
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Williams, G. J.
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Yoon, C. H.
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Zatsepin, N.
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Fromme, P.
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Duszenko, M.
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Chapman, H. N.
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Betzel, C.
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University of Gothenburg