Observation of substrate diffusion and ligand binding in enzyme crystals using high-repetition-rate mix-and-inject serial crystallography

Here, we illustrate what happens inside the catalytic cleft of an enzyme when substrate or ligand binds on single-millisecond timescales. The initial phase of the enzymatic cycle is observed with near-atomic resolution using the most advanced X-ray source currently available: the European XFEL (EuXF...

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Bibliographic Details
Published in:	IUCrJ Vol. 8; no. 6; pp. 878 - 895
Main Authors:	Pandey, Suraj, Calvey, George, Katz, Andrea M., Malla, Tek Narsingh, Koua, Faisal H. M., Martin-Garcia, Jose M., Poudyal, Ishwor, Yang, Jay-How, Vakili, Mohammad, Yefanov, Oleksandr, Zielinski, Kara A., Bajt, Sasa, Awel, Salah, Doerner, Katarina, Frank, Matthias, Gelisio, Luca, Jernigan, Rebecca, Kirkwood, Henry, Kloos, Marco, Koliyadu, Jayanath, Mariani, Valerio, Miller, Mitchell D., Mills, Grant, Nelson, Garrett, Olmos, Jose L., Sadri, Alireza, Sato, Tokushi, Tolstikova, Alexandra, Xu, Weijun, Ourmazd, Abbas, Spence, John C. H., Schwander, Peter, Barty, Anton, Chapman, Henry N., Fromme, Petra, Mancuso, Adrian P., Phillips, George N., Bean, Richard, Pollack, Lois, Schmidt, Marius
Format:	Journal Article
Language:	English
Published:	England International Union of Crystallography 01.11.2021 International Union of Crystallography (IUCr)
Subjects:	antibiotic resistance Binding ceftriaxone Crystal structure Crystallography Diffusion coefficient Diffusion rate drug discovery enzyme kinetics enzyme mechanisms Enzymes european x-ray free-electron laser irreversible inhibition Ligands megahertz pulse-repetition rate mix-and-inject serial crystallography protein structure determination Repetition Research Papers serial femtosecond crystallography substrate diffusion in crystals Substrates sulbactam Time lag Tuberculosis X ray sources x-ray crystallography β-lactamases β-lactamases megahertz pulse-repetition rate irreversible inhibition enzyme kinetics enzyme mechanisms sulbactam X-ray crystallography ceftriaxone mix-and-inject serial crystallography drug discovery antibiotic resistance substrate diffusion in crystals European X-ray Free-Electron Laser protein structure determination serial femtosecond crystallography
ISSN:	2052-2525, 2052-2525
Online Access:	Get full text
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