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Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.
Redecke, Lars; Nass, Karol; DePonte, Daniel P; White, Thomas A; Rehders, Dirk; Barty, Anton; Stellato, Francesco; Liang, Mengning; Barends, Thomas R M; Boutet, Sébastien; Williams, Garth J; Messerschmidt, Marc; Seibert, M Marvin; Aquila, Andrew; Arnlund, David; Bajt, Sasa; Barth, Torsten; Bogan, Michael J; Caleman, Carl; Chao, Tzu-Chiao; Doak, R Bruce; Fleckenstein, Holger; Frank, Matthias; Fromme, Raimund; Galli, Lorenzo; Grotjohann, Ingo; Hunter, Mark S; Johansson, Linda C; Kassemeyer, Stephan; Katona, Gergely; Kirian, Richard A; Koopmann, Rudolf; Kupitz, Chris; Lomb, Lukas; Martin, Andrew V; Mogk, Stefan; Neutze, Richard; Shoeman, Robert L; Steinbrener, Jan; Timneanu, Nicusor; Wang, Dingjie; Weierstall, Uwe; Zatsepin, Nadia A; Spence, John C H; Fromme, Petra; Schlichting, Ilme; Duszenko, Michael; Betzel, Christian; Chapman, Henry N.
Affiliation
  • 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), Notkestrasse 85, 22607 Hamburg, Germany.
  • Nass K; German Centre for Infection Research, University of Lübeck, 23538 Lübeck, Germany.
  • DePonte DP; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • White TA; Department of Physics, University of Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany.
  • Rehders D; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Barty A; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Stellato F; 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), Notkestrasse 85, 22607 Hamburg, Germany.
  • Liang M; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Barends TRM; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Boutet S; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Williams GJ; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.
  • Messerschmidt M; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Seibert MM; Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Aquila A; Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Arnlund D; Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Bajt S; Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Barth T; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Bogan MJ; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
  • Caleman C; Photon Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Chao TC; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany.
  • Doak RB; Photon Ultrafast Laser Science and Engineering (PULSE) Institute, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Fleckenstein H; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Frank M; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
  • Fromme R; Department of Physics, Arizona State University, Tempe, AZ 85287, USA.
  • Galli L; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Grotjohann I; Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550, USA.
  • Hunter MS; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
  • Johansson LC; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Kassemeyer S; Department of Physics, University of Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany.
  • Katona G; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
  • Kirian RA; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
  • Koopmann R; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
  • Kupitz C; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.
  • Lomb L; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Martin AV; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
  • Mogk S; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Neutze R; Department of Physics, Arizona State University, Tempe, AZ 85287, USA.
  • Shoeman RL; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany.
  • Steinbrener J; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
  • Timneanu N; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.
  • Wang D; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Weierstall U; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Zatsepin NA; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany.
  • Spence JCH; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
  • Fromme P; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.
  • Schlichting I; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Duszenko M; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.
  • Betzel C; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.
  • Chapman HN; Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, SE-75124 Uppsala, Sweden.
Science ; 339(6116): 227-230, 2013 Jan 11.
Article in En | MEDLINE | ID: mdl-23196907
ABSTRACT
The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the "diffraction-before-destruction" approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trypanosoma brucei brucei / Cathepsin B / Protozoan Proteins Limits: Animals Language: En Journal: Science Year: 2013 Type: Article Affiliation country: Germany
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trypanosoma brucei brucei / Cathepsin B / Protozoan Proteins Limits: Animals Language: En Journal: Science Year: 2013 Type: Article Affiliation country: Germany