TY  - EJOUR
AU  - Pandey, Suraj
AU  - Bean, Richard
AU  - Sato, Tokushi
AU  - Poudyal, Ishwor
AU  - Bielecki, Johan
AU  - Cruz Villarreal, Jorvani
AU  - Yefanov, Oleksandr
AU  - Mariani, Valerio
AU  - White, Thomas A.
AU  - Kupitz, Christopher
AU  - Hunter, Mark
AU  - Abdellatif, Mohamed H.
AU  - Bajt, Saša
AU  - Bondar, Valerii
AU  - Echelmeier, Austin
AU  - Doppler, Diandra
AU  - Emons, Moritz
AU  - Frank, Matthias
AU  - Fromme, Raimund
AU  - Gevorkov, Yaroslav
AU  - Giovanetti, Gabriele
AU  - Jiang, Man
AU  - Kim, Daihyun
AU  - Kim, Yoonhee
AU  - Kirkwood, Henry
AU  - Klimovskaia, Anna
AU  - Knoska, Juraj
AU  - Koua, Faisal H. M.
AU  - Letrun, Romain
AU  - Lisova, Stella
AU  - Maia, Luis
AU  - Mazalova, Victoria
AU  - Meza, Domingo
AU  - Michelat, Thomas
AU  - Ourmazd, Abbas
AU  - Palmer, Guido
AU  - Ramilli, Marco
AU  - Schubert, Robin
AU  - Schwander, Peter
AU  - Silenzi, Alessandro
AU  - Sztuk-Dambietz, Jolanta
AU  - Tolstikova, Alexandra
AU  - Chapman, Henry N.
AU  - Ros, Alexandra
AU  - Barty, Anton
AU  - Fromme, Petra
AU  - Mancuso, Adrian P.
AU  - Schmidt, Marius
TI  - Direct Observation of the Mechanism of Antibiotic Resistance by Mix-and-Inject at the European XFEL
PB  - biorXiv
M1  - PUBDB-2021-03253
PY  - 2020
N1  - Published in Nature Methods as: "Pandey, S., Bean, R., Sato, T. et al. Time-resolved serial femtosecond crystallography at the European XFEL. Nat Methods 17, 73–78 (2020). https://doi.org/10.1038/s41592-019-0628-z"
AB  - In this study, we follow the diffusion and buildup of occupancy of the substrate ceftriaxone in M. tuberculosis β-lactamase BlaC microcrystals by structural analysis of the enzyme substrate complex at single millisecond time resolution. We also show the binding and the reaction of an inhibitor, sulbactam, on a slower millisecond time scale. We use the ‘mix-and-inject’ technique to initiate these reactions by diffusion, and determine the resulting structures by serial crystallography using ultrafast, intense X-ray pulses from the European XFEL (EuXFEL) arriving at MHz repetition rates. Here, we show how to use the EuXFEL pulse structure to dramatically increase the size of the data set and thereby the quality and time resolution of “molecular movies” which unravel ligand binding and enzymatically catalyzed reactions. This shows the great potential for the EuXFEL as a tool for biomedically relevant research, particularly, as shown here, for investigating bacterial antibiotic resistance.
LB  - PUB:(DE-HGF)25
DO  - DOI:10.1101/2020.11.24.396689
UR  - https://bib-pubdb1.desy.de/record/462078
ER  -