Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.

Autor: 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.; German Centre for Infection Research, University of Lübeck, 23538 Lübeck, Germany., Nass K; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.; Department of Physics, University of Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany., DePonte DP; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., White TA; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., 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), Notkestrasse 85, 22607 Hamburg, Germany., Barty A; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Stellato F; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Liang M; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Barends TRM; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Boutet S; Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA., Williams GJ; Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA., Messerschmidt M; Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA., 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; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Arnlund D; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden., Bajt S; Photon Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany., Barth T; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany., Bogan MJ; Photon Ultrafast Laser Science and Engineering (PULSE) Institute, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA., Caleman C; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Chao TC; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA., Doak RB; Department of Physics, Arizona State University, Tempe, AZ 85287, USA., Fleckenstein H; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Frank M; Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550, USA., Fromme R; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA., Galli L; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.; Department of Physics, University of Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany., Grotjohann I; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA., Hunter MS; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA., Johansson LC; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden., Kassemeyer S; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Katona G; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden., Kirian RA; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.; Department of Physics, Arizona State University, Tempe, AZ 85287, USA., Koopmann R; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany., Kupitz C; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA., Lomb L; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Martin AV; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Mogk S; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany., Neutze R; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden., Shoeman RL; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Steinbrener J; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Timneanu N; Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, SE-75124 Uppsala, Sweden., Wang D; Department of Physics, Arizona State University, Tempe, AZ 85287, USA., Weierstall U; Department of Physics, Arizona State University, Tempe, AZ 85287, USA., Zatsepin NA; Department of Physics, Arizona State University, Tempe, AZ 85287, USA., Spence JCH; Department of Physics, Arizona State University, Tempe, AZ 85287, USA., Fromme P; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA., Schlichting I; Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany.; Max Planck Advanced Study Group, Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany., Duszenko M; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany., Betzel C; Institute of Biochemistry and Molecular Biology, University of Hamburg, at DESY, Notkestrasse 85, 22607 Hamburg, Germany., Chapman HN; Center for Free-Electron Laser Science (CFEL), DESY, Notkestrasse 85, 22607 Hamburg, Germany.; Department of Physics, University of Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2013 Jan 11; Vol. 339 (6116), pp. 227-230. Date of Electronic Publication: 2012 Nov 29.
DOI: 10.1126/science.1229663
Abstrakt: 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.
Databáze: MEDLINE