Publication Date:
2012-12-01
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786669/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Redecke, Lars -- Nass, Karol -- DePonte, Daniel P -- White, Thomas A -- Rehders, Dirk -- Barty, Anton -- Stellato, Francesco -- Liang, Mengning -- Barends, Thomas R M -- Boutet, Sebastien -- 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 -- 1R01GM095583/GM/NIGMS NIH HHS/ -- R01 GM095583/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 11;339(6116):227-30. doi: 10.1126/science.1229663. Epub 2012 Nov 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joint Laboratory for Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, and Institute of Biochemistry, University of Lubeck, at Deutsches Elektronen-Synchrotron, Notkestrasse 85, 22607 Hamburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23196907" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Catalytic Domain
;
Cathepsin B/antagonists & inhibitors/*chemistry
;
Crystallization
;
Crystallography, X-Ray
;
Enzyme Precursors/chemistry
;
Glycosylation
;
Models, Molecular
;
Molecular Sequence Data
;
Protein Conformation
;
Protozoan Proteins/antagonists & inhibitors/*chemistry
;
Sf9 Cells
;
Spodoptera
;
Trypanosoma brucei brucei/*enzymology
;
X-Rays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
