Five-dimensional crystallography

Schmidt, Marius; Graber, Tim; Henning, Robert H.; Šrajer, V.

doi:10.1107/s0108767309054166

Cited by 49 publications

(48 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When time-series are collected at different temperatures, they can be analyzed with the approach discussed above. As a result, the temperature dependence of the rate coefficients in the mechanism are extracted, which can be analyzed by equation above, and ΔH # and ΔS # determined from crystallographic data alone (Schmidt et al ., 2010; Schmidt et al ., 2013). The ΔH # is a measure of the energy change on top of the energy barrier, e.g.…”

Section: From Data To Structures Of Intermediates and Beyondmentioning

confidence: 99%

Watching proteins function with time-resolved x-ray crystallography

Šrajer

Schmidt

2017

J. Phys. D: Appl. Phys.

Self Cite

View full text Add to dashboard Cite

Macromolecular crystallography was immensely successful in the last two decades. To a large degree this success resulted from use of powerful third generation synchrotron X-ray sources. An expansive database of more than 100,000 protein structures, of which many were determined at resolution better than 2 Å, is available today. With this achievement, the spotlight in structural biology is shifting from determination of static structures to elucidating dynamic aspects of protein function. A powerful tool for addressing these aspects is time-resolved crystallography, where a genuine biological function is triggered in the crystal with a goal of capturing molecules in action and determining protein kinetics and structures of intermediates (Schmidt et al., 2005a; Schmidt 2008; Neutze and Moffat, 2012; Šrajer 2014). In this approach, short and intense X-ray pulses are used to probe intermediates in real time and at room temperature, in an ongoing reaction that is initiated synchronously and rapidly in the crystal. Time-resolved macromolecular crystallography with 100 ps time resolution at synchrotron X-ray sources is in its mature phase today, particularly for studies of reversible, light-initiated reactions. The advent of the new free electron lasers for hard X-rays (XFELs; 5–20 keV), which provide exceptionally intense, femtosecond X-ray pulses, marks a new frontier for time-resolved crystallography. The exploration of ultra-fast events becomes possible in high-resolution structural detail, on sub-picosecond time scales (Tenboer et al., 2014; Barends et al., 2015; Pande et al., 2016). We review here state-of-the-art time-resolved crystallographic experiments both at synchrotrons and XFELs. We also outline challenges and further developments necessary to broaden the application of these methods to many important proteins and enzymes of biomedical relevance.

show abstract

Section: From Data To Structures Of Intermediates and Beyondmentioning

confidence: 99%

Watching proteins function with time-resolved x-ray crystallography

Šrajer

Schmidt

2017

J. Phys. D: Appl. Phys.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because of this experimental requirement, a vast majority of time-resolved crystallography experiments have been performed on targets where a fast laser pulse can be used to trigger the reaction. Examples include photolysis-induced dissociation of CO from myoglobin 207,208 and the photocycles of photoactive yellow protein (PYP), 19,199,200,[209][210][211][212][213][214][215] photosystem II, 22,165-167 and bacteriorhodopsin. 174 It is also possible to use laser triggering to initiate a reaction through the photorelease of a caged compound.…”

Section: A Laser Triggeringmentioning

confidence: 99%

Microfluidics: From crystallization to serial time-resolved crystallography

Sui

Perry

2017

Structural Dynamics

View full text Add to dashboard Cite

Capturing protein structural dynamics in real-time has tremendous potential in elucidating biological functions and providing information for structure-based drug design. While time-resolved structure determination has long been considered inaccessible for a vast majority of protein targets, serial methods for crystallography have remarkable potential in facilitating such analyses. Here, we review the impact of microfluidic technologies on protein crystal growth and X-ray diffraction analysis. In particular, we focus on applications of microfluidics for use in serial crystallography experiments for the time-resolved determination of protein structural dynamics.

show abstract

“…At the BioCARS 14ID B beamline (APS), a single exposure with a 153 ps X-ray pulse from the synchrotron operated in the hybrid mode was used in a Laue diffraction experiment with the photoactive yellow protein (Schmidt et al 2010). Twenty-four Laue patterns were required for a complete dataset, with the crystal at different orientations between each exposure.…”

Section: Time-resolved Studiesmentioning

confidence: 99%

Macromolecular crystallography at synchrotron radiation sources: current status and future developments

Duke

Johnson

2010

Proc. R. Soc. A.

View full text Add to dashboard Cite

X-ray diffraction with synchrotron radiation (SR) has revealed the atomic structures of numerous biological macromolecules including proteins and protein complexes, nucleic acids and their protein complexes, viruses, membrane proteins and drug targets. The bright SR X-ray beam with its small divergence has made the study of weakly diffracting crystals of large biological molecules possible. The ability to tune the wavelength of the SR beam to the absorption edge of certain elements has allowed anomalous scattering to be exploited for phase determination. We review the developments at synchrotron sources and beamlines from the early days to the present time, and discuss the significance of the results in providing a deeper understanding of the biological function, the design of new therapeutic molecules and time-resolved studies of dynamic events using pump-probe techniques. Radiation damage, a problem with bright X-ray sources, has been partially alleviated by collecting data at low temperature (100 K) but work is ongoing. In the most recent development, free electron laser sources can offer a peak brightness of hard X-rays approximately 10 8 times brighter than that achieved at SR sources. We describe briefly how early experiments at FLASH and Linear Coherent Light Source have shown exciting possibilities for the future.

show abstract

Five-dimensional crystallography

Cited by 49 publications

References 40 publications

Watching proteins function with time-resolved x-ray crystallography

Watching proteins function with time-resolved x-ray crystallography

Microfluidics: From crystallization to serial time-resolved crystallography

Macromolecular crystallography at synchrotron radiation sources: current status and future developments

Contact Info

Product

Resources

About