Mix-and-diffuse serial synchrotron crystallography

被引:108
作者
Beyerlein, Kenneth R. [1 ]
Dierksmeyer, Dennis [2 ]
Mariani, Valerio [1 ]
Kuhn, Manuela [2 ]
Sarrou, Iosifina [1 ]
Ottaviano, Angelica [3 ]
Awel, Salah [1 ,4 ]
Knoska, Juraj [1 ,5 ]
Fuglerud, Silje [1 ,6 ]
Jonsson, Olof [7 ]
Stern, Stephan [1 ,8 ]
Wiedorn, Max O. [1 ,5 ]
Yefanov, Oleksandr [1 ]
Adriano, Luigi [2 ]
Bean, Richard [1 ]
Burkhardt, Anja [2 ]
Fischer, Pontus [2 ]
Heymann, Michael [1 ]
Horke, Daniel A. [1 ,4 ]
Jungnickel, Katharina E. J. [9 ]
Kovaleva, Elena [10 ]
Lorbeer, Olga [2 ]
Metz, Markus [1 ]
Meyer, Jan [2 ]
Morgan, Andrew [1 ]
Pande, Kanupriya [1 ]
Panneerselvam, Saravanan [2 ]
Seuring, Carolin [1 ,4 ]
Tolstikova, Aleksandra [1 ]
Lieske, Julia [2 ]
Aplin, Steve [1 ]
Roessle, Manfred [11 ]
White, Thomas A. [1 ]
Chapman, Henry N. [1 ,4 ,5 ]
Meents, Alke [1 ,2 ]
Oberthuer, Dominik [1 ]
机构
[1] Deutsch Elektronen Synchrotron DESY, Ctr Free Elect Laser Sci, Notkestr 85, D-22607 Hamburg, Germany
[2] Deutsch Elektronen Synchrotron DESY, Photon Sci, Hamburg, Germany
[3] Calif State Univ Northridge, Dept Phys, Northridge, CA 91330 USA
[4] Univ Hamburg, Hamburg Ctr Ultrafast Imaging, D-22761 Hamburg, Germany
[5] Univ Hamburg, Dept Phys, Luruper Chaussee 149, D-22607 Hamburg, Germany
[6] Norwegian Univ Sci & Technol, Dept Phys, Trondheim, Norway
[7] Uppsala Univ, Dept Phys & Astron, Uppsala, Sweden
[8] European Xray Free Elect Laser Facil GmbH XFEL, Schenefeld, Germany
[9] Univ Oxford, Dept Biochem, Oxford, England
[10] SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA USA
[11] Fachhsch Lubeck, Lubeck, Germany
基金
欧洲研究理事会;
关键词
drug discovery; protein structure; X-ray crystallography; serial crystallography; time-resolved studies; lysozyme; EGG-WHITE LYSOZYME; MILLISECOND CRYSTALLOGRAPHY; CRYSTAL-STRUCTURE; INHIBITORS; CATALYSIS; DYNAMICS; BINDING;
D O I
10.1107/S2052252517013124
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. The success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.
引用
收藏
页码:769 / 777
页数:9
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