Evidence map›Paper›PMID 29848358›Full record

ArticleBMC biology2018

Enzyme intermediates captured "on the fly" by mix-and-inject serial crystallography.

Jose L Olmos, Suraj Pandey, Jose M Martin-Garcia, George Calvey, Andrea Katz, Juraj Knoska, Christopher Kupitz, Mark S Hunter, Mengning Liang, Dominik Oberthuer and 40 more

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 166 citations in OpenAlex.

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  7. Glyoxalase activities of Parkinson's disease relevant protein DJ-1/PARK7: Past discoveries and future perspectives.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2026
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43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

50 authors at 12 institutions in 4 countries.

Jose L OlmosDepartment of BioSciences, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
Suraj PandeyPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
Jose M Martin-GarciaSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
George CalveySchool of Applied and Engineering Physics, Cornell University, 254 Clark Hall, Ithaca, NY, 14853, USA.
Andrea KatzSchool of Applied and Engineering Physics, Cornell University, 254 Clark Hall, Ithaca, NY, 14853, USA.
Juraj KnoskaCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Christopher KupitzPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
Mark S HunterLinac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National, Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
Mengning LiangLinac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National, Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
Dominik OberthuerCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Oleksandr YefanovCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Max WiedornCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Michael HeymanMax Planck Institut fuer Biochemie, Am Klopferspitz 18, 82152, Planegg, Germany.
Mark HollSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
Kanupriya PandeLawrence Berkeley National Lab, 1 Cyclotron Road, Berkeley, CA, 94720, USA.
Anton BartyCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Mitchell D MillerDepartment of BioSciences, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
Stephan SternCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Shatabdi Roy-ChowdhurySchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
Jesse CoeSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
Nirupa NagaratnamSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
James ZookSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
Jacob VerburgtPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
Tyler NorwoodPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
Ishwor PoudyalPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
David XuDepartment of BioSciences, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
Jason KoglinLinac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National, Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
Matthew H SeabergLinac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National, Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA, 94025, USA.
Yun ZhaoSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
Saša BajtPhoton Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Thomas GrantUniversity of New York Buffalo, Hauptman-Woodward Institute, 700 Ellicott St, Buffalo, NY, 14203, USA.
Valerio MarianiCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Garrett NelsonDepartment of Physics, Arizona State University, Tempe, AZ, 85287, USA.
Ganesh SubramanianDepartment of Physics, Arizona State University, Tempe, AZ, 85287, USA.
Euiyoung BaeDepartment of Agricultural Biotechnology, Seoul National University, Seoul, 08826, Korea.
Raimund FrommeSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
Russell FungPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
Peter SchwanderPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
Matthias FrankLawrence Livermore National Laboratory, Livermore, CA, 94550, USA.
Thomas A WhiteCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Uwe WeierstallDepartment of Physics, Arizona State University, Tempe, AZ, 85287, USA.
Nadia ZatsepinDepartment of Physics, Arizona State University, Tempe, AZ, 85287, USA.
John SpenceDepartment of Physics, Arizona State University, Tempe, AZ, 85287, USA.
Petra FrommeSchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ, 85287-1604, USA.
Henry N ChapmanCenter for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Lois PollackSchool of Applied and Engineering Physics, Cornell University, 254 Clark Hall, Ithaca, NY, 14853, USA.
Lee Tremblay4Marbles Inc., 1900 Belvedere Pl, Westfield, IN, 46074, USA.
Abbas OurmazdPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA.
George N PhillipsDepartment of BioSciences, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
Marius SchmidtPhysics Department, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI, 53211, USA. m-schmidt@uwm.edu.ORCID 0000-0002-0962-9468
Arizona State University · USUniversität Hamburg · DEUniversity of Wisconsin–Milwaukee · USRice University · USSLAC National Accelerator Laboratory · USCornell University · USGlaxoSmithKline (United Kingdom) · GBHauptman-Woodward Medical Research Institute · USLawrence Berkeley National Laboratory · USLawrence Livermore National Laboratory · USMax Planck Institute of Biochemistry · DESeoul National University · KR

Funding

Technology development for biological imaging with x-ray free electron lasersR01GM117342 · NIGMS · LAWRENCE LIVERMORE NATIONAL SECURITY, LLC · PI FRANK, MATTHIAS · 2016 to 2024
$4.8M
Femtosecond nano-crystallography of membrane proteinsR01GM095583 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI FROMME, PETRA · 2010 to 2023
$4.3M
NIGMS NIH HHS R01 GM095583NIGMS NIH HHS R01 GM117342
6 · The paper itself

Abstract

backgroundEver 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.

resultsHere, 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.

conclusionsMISC 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.

Indexed as

Anti-Bacterial AgentsBacterial Proteinsbeta-LactamasesBiocatalysisCeftriaxoneCephalosporin ResistanceCrystallography, X-RayKineticsLasersModels, MolecularMycobacterium tuberculosisTime FactorsAnti-Bacterial AgentsBacterial Proteinsbeta-LactamasesCeftriaxone

Identifiers

PMID29848358
PMCPMC5977757
OpenAlexW2805692389

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.