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Buffalo, NY, United States

Feld G.K.,Lawrence Livermore National Laboratory | Feld G.K.,National Health Research Institute | Heymann M.,Brandeis University | Heymann M.,University of Hamburg | And 20 more authors.
Journal of Applied Crystallography | Year: 2015

X-ray free-electron lasers (XFELs) offer a new avenue to the structural probing of complex materials, including biomolecules. Delivery of precious sample to the XFEL beam is a key consideration, as the sample of interest must be serially replaced after each destructive pulse. The fixed-target approach to sample delivery involves depositing samples on a thin-film support and subsequent serial introduction via a translating stage. Some classes of biological materials, including two-dimensional protein crystals, must be introduced on fixed-target supports, as they require a flat surface to prevent sample wrinkling. A series of wafer and transmission electron microscopy (TEM)-style grid supports constructed of low-Z plastic have been custom-designed and produced. Aluminium TEM grid holders were engineered, capable of delivering up to 20 different conventional or plastic TEM grids using fixed-target stages available at the Linac Coherent Light Source (LCLS). As proof-of-principle, X-ray diffraction has been demonstrated from two-dimensional crystals of bacteriorhodopsin and three-dimensional crystals of anthrax toxin protective antigen mounted on these supports at the LCLS. The benefits and limitations of these low-Z fixed-target supports are discussed; it is the authors' belief that they represent a viable and efficient alternative to previously reported fixed-target supports for conducting diffraction studies with XFELs. © 2015 International Union of Crystallography. Source


Beyerlein K.R.,German Electron Synchrotron | Jooss C.,University of Gottingen | Barty A.,German Electron Synchrotron | Bean R.,German Electron Synchrotron | And 26 more authors.
Powder Diffraction | Year: 2015

We report on the analysis of virtual powder-diffraction patterns from serial femtosecond crystallography (SFX) data collected at an X-ray free-electron laser. Different approaches to binning and normalizing these patterns are discussed with respect to the microstructural characteristics which each highlights. Analysis of SFX data from a powder of Pr0.5Ca0.5MnO3 in this way finds evidence of other trace phases in its microstructure which was not detectable in a standard powder-diffraction measurement. Furthermore, a comparison between two virtual powder pattern integration strategies is shown to yield different diffraction peak broadening, indicating sensitivity to different types of microstrain. This paper is a first step in developing new data analysis methods for microstructure characterization from serial crystallography data. Copyright © International Centre for Diffraction Data 2014. Source


Beyerlein K.R.,German Electron Synchrotron | Jooss C.,University of Gottingen | Barty A.,German Electron Synchrotron | Bean R.,German Electron Synchrotron | And 26 more authors.
Powder Diffraction | Year: 2014

We report on the analysis of virtual powder-diffraction patterns from serial femtosecond crystallography (SFX) data collected at an X-ray free-electron laser. Different approaches to binning and normalizing these patterns are discussed with respect to the microstructural characteristics which each highlights. Analysis of SFX data from a powder of Pr0.5Ca0.5MnO3 in this way finds evidence of other trace phases in its microstructure which was not detectable in a standard powder-diffraction measurement. Furthermore, a comparison between two virtual powder pattern integration strategies is shown to yield different diffraction peak broadening, indicating sensitivity to different types of microstrain. This paper is a first step in developing new data analysis methods for microstructure characterization from serial crystallography data. © 2014 International Centre for Diffraction Data. Source


Liang M.,SLAC | Williams G.J.,SLAC | Williams G.J.,Brookhaven National Laboratory | Messerschmidt M.,SLAC | And 19 more authors.
Journal of Synchrotron Radiation | Year: 2015

The Coherent X-ray Imaging (CXI) instrument specializes in hard X-ray, in-vacuum, high power density experiments in all areas of science. Two main sample chambers, one containing a 100nm focus and one a 1μm focus, are available, each with multiple diagnostics, sample injection, pump-probe and detector capabilities. The flexibility of CXI has enabled it to host a diverse range of experiments, from biological to extreme matter. Source


Zhang H.,University of Southern California | Unal H.,Cleveland Clinic | Gati C.,German Electron Synchrotron | Han G.W.,University of Southern California | And 25 more authors.
Cell | Year: 2015

Angiotensin II type 1 receptor (AT1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT1R blockers (ARBs), the structural basis for AT1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high-quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT1R in complex with its selective antagonist ZD7155 at 2.9-Å resolution. The AT1R-ZD7155 complex structure revealed key structural features of AT1R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT1R structure-function relationship and structure-based drug design. © 2015 Elsevier Inc. Source

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