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

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dc.citation.articleNumber59en_US
dc.citation.journalTitleBMC Biologyen_US
dc.citation.volumeNumber16en_US
dc.contributor.authorOlmos, Jose Luis Jr.en_US
dc.contributor.authorPandey, Surajen_US
dc.contributor.authorMartin-Garcia, Jose M.en_US
dc.contributor.authorCalvey, Georgeen_US
dc.contributor.authorKatz, Andreaen_US
dc.contributor.authorKnoska, Jurajen_US
dc.contributor.authorKupitz, Christopheren_US
dc.contributor.authorHunter, Mark S.en_US
dc.contributor.authorLiang, Mengningen_US
dc.contributor.authorOberthuer, Dominiken_US
dc.contributor.authorYefanov, Oleksandren_US
dc.contributor.authorWiedorn, Maxen_US
dc.contributor.authorHeyman, Michaelen_US
dc.contributor.authorHoll, Marken_US
dc.contributor.authorPande, Kanupriyaen_US
dc.contributor.authorBarty, Antonen_US
dc.contributor.authorMiller, Mitchell D.en_US
dc.contributor.authorStern, Stephanen_US
dc.contributor.authorRoy-Chowdhury, Shatabdien_US
dc.contributor.authorCoe, Jesseen_US
dc.contributor.authorNagaratnam, Nirupaen_US
dc.contributor.authorZook, Jamesen_US
dc.contributor.authorVerburgt, Jacoben_US
dc.contributor.authorNorwood, Tyleren_US
dc.contributor.authorPoudyal, Ishworen_US
dc.contributor.authorXu, Daviden_US
dc.contributor.authorKoglin, Jason E.en_US
dc.contributor.authorSeaberg, Matthew H.en_US
dc.contributor.authorZhao, Yunen_US
dc.contributor.authorBajt, Sašaen_US
dc.contributor.authorGrant, Thomasen_US
dc.contributor.authorMariani, Valerioen_US
dc.contributor.authorNelson, Garretten_US
dc.contributor.authorSubramanian, Ganeshen_US
dc.contributor.authorBae, Euiyoungen_US
dc.contributor.authorFromme, Raimunden_US
dc.contributor.authorFung, Russellen_US
dc.contributor.authorSchwander, Peteren_US
dc.contributor.authorFrank, Matthiasen_US
dc.contributor.authorWhite, Thomas A.en_US
dc.contributor.authorWeierstall, Uween_US
dc.contributor.authorZatsepin, Nadiaen_US
dc.contributor.authorSpence, Johnen_US
dc.contributor.authorFromme, Petraen_US
dc.contributor.authorChapman, Henry N.en_US
dc.contributor.authorPollack, Loisen_US
dc.contributor.authorTremblay, Leeen_US
dc.contributor.authorOurmazd, Abbasen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.contributor.authorSchmidt, Mariusen_US
dc.date.accessioned2018-09-26T14:52:43Zen_US
dc.date.available2018-09-26T14:52:43Zen_US
dc.date.issued2018en_US
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.en_US
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.en_US
dc.identifier.digitals12915-018-0524-5en_US
dc.identifier.doihttps://doi.org/10.1186/s12915-018-0524-5en_US
dc.identifier.urihttps://hdl.handle.net/1911/102714en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
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.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleEnzyme intermediates captured “on the fly” by mix-and-inject serial crystallographyen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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