Showing papers by "Karol Nass published in 2023"
TL;DR: In this article , the authors used time-resolved serial crystallography at a synchrotron and X-ray free-electron laser to capture the release of the anti-cancer compound azo-combretastatin A4 and the resulting conformational changes in tubulin.
Abstract: The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology. Using time-resolved serial crystallography at a synchrotron and X-ray free-electron laser, we capture the release of the anti-cancer compound azo-combretastatin A4 and the resulting conformational changes in tubulin. Nine structural snapshots from 1 ns to 100 ms complemented by simulations show how cis-to-trans isomerization of the azobenzene bond leads to a switch in ligand affinity, opening of an exit channel, and collapse of the binding pocket upon ligand release. The resulting global backbone rearrangements are related to the action mechanism of microtubule-destabilizing drugs.
2 citations
TL;DR: In this paper , the authors used hard x-ray free-electron laser (FEL) pulses, which are chirped both in photon energy and in spatial position.
Abstract: We have produced hard x-ray free-electron laser (FEL) pulses, which are chirped both in photon energy and in spatial position. The experiments have been carried out at the hard x-ray beamline Aramis at SwissFEL, located at the Paul Scherrer Institute in Switzerland. The FEL beamline was operated without any external focusing and with a tilted, energy-chirped electron bunch, whose properties are then transferred to the photon beam. The resulting FEL pulses were used for a single-shot absorption x-ray spectroscopy experiment at the Alvra endstation. But, as will be outlined, applications of this type of tailored FEL pulse go beyond such experiments, allowing for x-ray pulse compression and control of the transverse coherence within the pulse.Received 13 May 2022Accepted 22 February 2023DOI:https://doi.org/10.1103/PhysRevResearch.5.L022009Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Physical SystemsFree-electron lasersAccelerators & Beams