Evidence map›Paper›PMID 34294694›Full record

ArticleNature communications2021

An on-demand, drop-on-drop method for studying enzyme catalysis by serial crystallography.

Agata Butryn, Philipp S Simon, Pierre Aller, Philip Hinchliffe, Ramzi N Massad, Gabriel Leen, Catherine L Tooke, Isabel Bogacz, In-Sik Kim, Asmit Bhowmick and 26 more

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
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

45 citing papers in PubMed.

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  12. Microfluidic Devices for High-Throughput In Situ Serial Crystallography.Advances in biochemical engineering/biotechnology · 2026
    Review
  13. Article
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  17. bioRxiv : the preprint server for biology · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Agata Butryn *Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0002-5227-4770
Philipp S Simon *Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0002-2859-4475
Pierre Aller *Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0002-1793-7030
Philip HinchliffeSchool of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol, UK.
Ramzi N MassadMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Gabriel LeenPolyPico Technologies Ltd, Unit 10, Airways Technology Park, Rathmacullig West, Cork, Ireland.
Catherine L TookeSchool of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol, UK.
Isabel BogaczMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
In-Sik KimMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Asmit BhowmickMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Aaron S BrewsterMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0002-0908-7822
Nicholas E DevenishDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.
Jürgen BremDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.ORCID 0000-0002-0137-3226
Jos J A G KampsDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.ORCID 0000-0001-8646-1796
Pauline A LangDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.ORCID 0000-0003-3187-1469
Patrick RabeDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Danny AxfordDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0001-7694-8525
John H BealeDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.
Bradley DavyDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.
Ali EbrahimDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.
Julien OrlansDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0002-6933-2287
Selina L S StormDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0001-9223-5576
Tiankun ZhouDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.
Shigeki OwadaRIKEN SPring-8 Center, Hyogo, Japan.
Rie TanakaRIKEN SPring-8 Center, Hyogo, Japan.
Kensuke TonoRIKEN SPring-8 Center, Hyogo, Japan.
Gwyndaf EvansDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0002-6079-2201
Robin L OwenDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0002-2104-7057
Frances A HouleChemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Nicholas K SauterMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0003-2786-6552
Christopher J SchofieldDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.ORCID 0000-0002-0290-6565
James SpencerSchool of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol, UK.ORCID 0000-0002-4602-0571
Vittal K YachandraMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Junko YanoMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0001-6308-9071
Jan F KernMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. jfkern@lbl.gov.ORCID 0000-0002-7272-1603
Allen M OrvilleDiamond Light Source, Harwell Science and Innovation Campus, Didcot, UK. allen.orville@diamond.ac.uk.ORCID 0000-0002-7803-1777

Funding

Taking Snapshots of the Water-Oxidation Reaction by the Mn4Ca Oxygen-Evolving Complex Using X-ray Crystallography and SpectroscopyR01GM055302 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI YACHANDRA, VITTAL · 1997 to 2022
$9.1M
DIALS: New Computational Methods to Enable Challenging Crystallographic ExperimentsR01GM117126 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI SAUTER, NICHOLAS K · 2016 to 2023
$6.1M
Biological Spectroscopy and Crystallography Using an X-ray Free Electron Laser - Supplemental EquipmentR01GM110501 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Junko Yano · 2014 to 2026
$4.8M
High throughput sample delivery method for time resolved studies of enzyme reactions with X-ray and complementary techniquesR01GM126289 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI KERN, JAN F · 2017 to 2025
$4.6M
Structure and Function of the Mn Oxygen-Evolving ComplexR56GM055302 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI YACHANDRA, VITTAL · 2009 to 2009
$530k
Quantum refinement for improvement of metalloenzyme crystal structuresF32GM133081 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI SUTHERLIN, KYLE D. · 2019 to 2019
$48k
Biotechnology and Biological Sciences Research Council 102593Biotechnology and Biological Sciences Research Council BB/J014400/1Cancer Research UK 24759NIGMS NIH HHS F32 GM133081NIGMS NIH HHS R01 GM055302NIGMS NIH HHS R01 GM110501NIGMS NIH HHS R01 GM117126NIGMS NIH HHS R01 GM126289NIGMS NIH HHS R56 GM055302Wellcome TrustWellcome Trust 210734/Z/18/Z
6 · The paper itself

Abstract

Serial femtosecond crystallography has opened up many new opportunities in structural biology. In recent years, several approaches employing light-inducible systems have emerged to enable time-resolved experiments that reveal protein dynamics at high atomic and temporal resolutions. However, very few enzymes are light-dependent, whereas macromolecules requiring ligand diffusion into an active site are ubiquitous. In this work we present a drop-on-drop sample delivery system that enables the study of enzyme-catalyzed reactions in microcrystal slurries. The system delivers ligand solutions in bursts of multiple picoliter-sized drops on top of a larger crystal-containing drop inducing turbulent mixing and transports the mixture to the X-ray interaction region with temporal resolution. We demonstrate mixing using fluorescent dyes, numerical simulations and time-resolved serial femtosecond crystallography, which show rapid ligand diffusion through microdroplets. The drop-on-drop method has the potential to be widely applicable to serial crystallography studies, particularly of enzyme reactions with small molecule substrates.

Indexed as

AnimalsAvian ProteinsBacterial Proteinsbeta-LactamasesBiocatalysisCatalytic DomainChickensCrystallography, X-RayEnzymesEquipment DesignModels, MolecularMuramidaseRecombinant ProteinsAvian ProteinsBacterial Proteinsbeta-lactamase CTX-M-15beta-LactamasesEnzymeshen egg lysozymeMuramidaseRecombinant Proteins

Identifiers

PMID34294694
PMCPMC8298390

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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.