Enzyme intermediates captured “on the fly” by mix-and-inject serial crystallography

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dc.citation.articleNumber59
dc.citation.journalTitleBMC Biology
dc.citation.volumeNumber16
dc.contributor.authorOlmos, Jose Luis Jr.
dc.contributor.authorPandey, Suraj
dc.contributor.authorMartin-Garcia, Jose M.
dc.contributor.authorCalvey, George
dc.contributor.authorKatz, Andrea
dc.contributor.authorKnoska, Juraj
dc.contributor.authorKupitz, Christopher
dc.contributor.authorHunter, Mark S.
dc.contributor.authorLiang, Mengning
dc.contributor.authorOberthuer, Dominik
dc.contributor.authorYefanov, Oleksandr
dc.contributor.authorWiedorn, Max
dc.contributor.authorHeyman, Michael
dc.contributor.authorHoll, Mark
dc.contributor.authorPande, Kanupriya
dc.contributor.authorBarty, Anton
dc.contributor.authorMiller, Mitchell D.
dc.contributor.authorStern, Stephan
dc.contributor.authorRoy-Chowdhury, Shatabdi
dc.contributor.authorCoe, Jesse
dc.contributor.authorNagaratnam, Nirupa
dc.contributor.authorZook, James
dc.contributor.authorVerburgt, Jacob
dc.contributor.authorNorwood, Tyler
dc.contributor.authorPoudyal, Ishwor
dc.contributor.authorXu, David
dc.contributor.authorKoglin, Jason E.
dc.contributor.authorSeaberg, Matthew H.
dc.contributor.authorZhao, Yun
dc.contributor.authorBajt, Saša
dc.contributor.authorGrant, Thomas
dc.contributor.authorMariani, Valerio
dc.contributor.authorNelson, Garrett
dc.contributor.authorSubramanian, Ganesh
dc.contributor.authorBae, Euiyoung
dc.contributor.authorFromme, Raimund
dc.contributor.authorFung, Russell
dc.contributor.authorSchwander, Peter
dc.contributor.authorFrank, Matthias
dc.contributor.authorWhite, Thomas A.
dc.contributor.authorWeierstall, Uwe
dc.contributor.authorZatsepin, Nadia
dc.contributor.authorSpence, John
dc.contributor.authorFromme, Petra
dc.contributor.authorChapman, Henry N.
dc.contributor.authorPollack, Lois
dc.contributor.authorTremblay, Lee
dc.contributor.authorOurmazd, Abbas
dc.contributor.authorPhillips, George N.Jr.
dc.contributor.authorSchmidt, Marius
dc.date.accessioned2018-09-26T14:52:43Z
dc.date.available2018-09-26T14:52:43Z
dc.date.issued2018
dc.description.abstractBACKGROUND: Ever since the first atomic structure of an enzyme was solved, the discovery of the mechanism and dynamics of reactions catalyzed by biomolecules has been the key goal for the understanding of the molecular processes that drive life on earth. Despite a large number of successful methods for trapping reaction intermediates, the direct observation of an ongoing reaction has been possible only in rare and exceptional cases. RESULTS: Here, we demonstrate a general method for capturing enzyme catalysis "in action" by mix-and-inject serial crystallography (MISC). Specifically, we follow the catalytic reaction of the Mycobacterium tuberculosis β-lactamase with the third-generation antibiotic ceftriaxone by time-resolved serial femtosecond crystallography. The results reveal, in near atomic detail, antibiotic cleavage and inactivation from 30 ms to 2 s. CONCLUSIONS: MISC is a versatile and generally applicable method to investigate reactions of biological macromolecules, some of which are of immense biological significance and might be, in addition, important targets for structure-based drug design. With megahertz X-ray pulse rates expected at the Linac Coherent Light Source II and the European X-ray free-electron laser, multiple, finely spaced time delays can be collected rapidly, allowing a comprehensive description of biomolecular reactions in terms of structure and kinetics from the same set of X-ray data.
dc.identifier.citationOlmos, Jose Luis Jr., Pandey, Suraj, Martin-Garcia, Jose M., et al.. "Enzyme intermediates captured “on the fly” by mix-and-inject serial crystallography." <i>BMC Biology,</i> 16, (2018) Springer Nature: https://doi.org/10.1186/s12915-018-0524-5.
dc.identifier.digitals12915-018-0524-5
dc.identifier.doihttps://doi.org/10.1186/s12915-018-0524-5
dc.identifier.urihttps://hdl.handle.net/1911/102714
dc.language.isoeng
dc.publisherSpringer Nature
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleEnzyme intermediates captured “on the fly” by mix-and-inject serial crystallography
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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