Search Results

You searched for all publications:

with publication states 'Published (Approved)'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

9 items found (0 items not approved), displaying all items.1

Instruments / Technical Area	Publication Details	Published
	The single-particle, clusters and biomolecules and serial femtosecond crystallography instrument of the European X-ray Free-Electron Laser: Interaction region downstream at atmospheric pressure (IRD) Adam Round , Pierre Aller , Richard Bean , Johan Bielecki , Agata Butryn , Nicholas E. Devenish , Raphael De Wijn , Thomas Dietze , Katerina Doerner , Fabio Dall'Antonia , Gabriele Giovanetti , Huijong Han , Vincent Hennicke , Chan Kim , Yoonhee Kim , Marco Kloos , Jayanath C. P. Koliyadu , Gabriel Leen , Romain Letrun , Luis Lopez Morillo , Allen M. Orville , Tim Pakendorf , Marco Ramilli , Nadja Reimers , Patrick Reinke , Juan Sanchez-Weatherby , Tokushi Sato , Robin Schubert , Joachim Schulz , Cedric Signe Takem , Marcin Sikorski , Prasad Thute , Fabian Trost , Oleksii Turkot , Patrik Vagovic , Mohammad Vakili , Raul Villanueva Guerrero , Henry N. Chapman , Alke Meents , Serguei Molodtsov , Sakura Pascarelli , Thomas Tschentschera , Adrian Mancuso , Pontus Fischer , Sebastian Guenther Journal Of Synchrotron Radiation 33 DOI: 10.1107/S1600577525008999 Open Access Show Abstract ▼ Abstract: The Single-Particle, Clusters and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) scientific instrument at the European X-Ray Free-Electron Laser (EuXFEL) became operational with user experiments in September 2017. The unique properties and capabilities of the EuXFEL, enabling megahertz data collection rates, provide more rapid data collection with improved statistics compared with other XFEL facilities. This improves the feasibility of obtaining multiple data points in time-resolved experiments and hence enables the observation of reactions in greater detail (molecular movies). In collaboration with the SFX User Consortium (SFX UC), the SPB/SFX instrument was designed to further increase user access and research outcomes. Focusing the pulses downstream of the first interaction region [described previously (Mancuso et al., 2019)], a second experiment plane is enabled, which allows for greater optimization and more efficient usage of available beam time. Additionally, the SFX UC provided further instrumentation to provide improved capabilities on SPB/SFX. The aim for additional and extended functionality for the second interaction region was to enable sample-efficient data collection at atmospheric pressure in an environment where the sample temperature and humidity can be controlled. This paper describes the extended capabilities of the downstream interaction region of the SPB/SFX instrument and its major components, in particular its X-ray focusing optics, vacuum to atmospheric pressure out-coupling, available sample delivery methods and 2D detector, and the supporting optical laser systems for pump–probe experiments.	Nov 2025
	Pr and Pfr structures of plant phytochrome A Soshichiro Nagano , David Von Stetten , Kaoling Guan , Peng-Yuan Chen , Chen Song , Thomas Barends , Manfred S. Weiss , Christian G. Feiler , Katerina Dörner , Iñaki De Diego Martinez , Robin Schubert , Johan Bielecki , Lea Brings , Huijong Han , Konstantin Kharitonov , Chan Kim , Marco Kloos , Jayanath C. P. Koliyadu , Faisal H. M. Koua , Ekaterina Round , Abhisakh Sarma , Tokushi Sato , Christina Schmidt , Joana Valerio , Agnieszka Wrona , Joachim Schulz , Raphael De Wijn , Romain Letrun , Richard Bean , Adrian Mancuso , Karsten Heyne , Jon Hughes Nature Communications 16 DOI: 10.1038/s41467-025-60738-w Open Access Show Abstract ▼ Abstract: Phytochromes are biliprotein photoreceptors widespread amongst microorganisms and ubiquitous in plants where they control developmental processes as diverse as germination, stem elongation and floral induction through the photoconversion of inactive Pr to the Pfr signalling state. Here we report crystal structures of the chromophore-binding module of soybean phytochrome A, including ~2.2 Å XFEL structures of Pr and Pfr at ambient temperature and high resolution cryogenic structures of Pr. In the Pfr structure, the chromophore is exposed to the medium, the D-ring remaining α-facial following the likely clockwise photoflip. The chromophore shifts within its pocket, while its propionate side chains, their partners as well as three neighbouring tyrosines shift radically. Helices near the chromophore show substantial shifts that might represent components of the light signal. These changes reflect those in bacteriophytochromes despite their quite different signalling mechanisms, implying that fundamental aspects of phytochrome photoactivation have been repurposed for photoregulation in the eukaryotic plant.	Jun 2025
I19-Small Molecule Single Crystal Diffraction	Ligand-mediated quantum yield enhancement in 1-D silver organothiolate metal–organic chalcogenolates Mariya Aleksich , Yeongsu Cho , Daniel W. Paley , Maggie C. Willson , Hawi N. Nyiera , Patience A. Kotei , Vanessa Oklejas , David W. Mittan-Moreau , Elyse A. Schriber , Kara Christensen , Ichiro Inoue , Shigeki Owada , Kensuke Tono , Michihiro Sugahara , Satomi Inaba-Inoue , Mohammad Vakili , Christopher J. Milne , Fabio Dallantonia , Dmitry Khakhulin , Fernando Ardana-Lamas , Frederico Lima , Joana Valerio , Huijong Han , Tamires Gallo , Hazem Yousef , Oleksii Turkot , Ivette J. Bermudez Macias , Thomas Kluyver , Philipp Schmidt , Luca Gelisio , Adam R. Round , Yifeng Jiang , Doriana Vinci , Yohei Uemura , Marco Kloos , Adrian P. Mancuso , Mark Warren , Nicholas K. Sauter , Jing Zhao , Tess Smidt , Heather J. Kulik , Sahar Sharifzadeh , Aaron S. Brewster , J. Nathan Hohman Advanced Functional Materials 17 DOI: 10.1002/adfm.202414914 Diamond Proposal Number(s): [35300] Show Abstract ▼ Abstract: X-ray free electron laser (XFEL) microcrystallography and synchrotron single-crystal crystallography are used to evaluate the role of organic substituent position on the optoelectronic properties of metal–organic chalcogenolates (MOChas). MOChas are crystalline 1D and 2D semiconducting hybrid materials that have varying optoelectronic properties depending on composition, topology, and structure. While MOChas have attracted much interest, small crystal sizes impede routine crystal structure determination. A series of constitutional isomers where the aryl thiol is functionalized by either methoxy or methyl ester are solved by small molecule serial femtosecond X-ray crystallography (smSFX) and single crystal rotational crystallography. While all the methoxy examples have a low quantum yield (0-1%), the methyl ester in the ortho position yields a high quantum yield of 22%. The proximity of the oxygen atoms to the silver inorganic core correlates to a considerable enhancement of quantum yield. Four crystal structures are solved at a resolution range of 0.8–1.0 Å revealing a collapse of the 2D topology for functional groups in the 2- and 3- positions, resulting in needle-like crystals. Further analysis using density functional theory (DFT) and many-body perturbation theory (MBPT) enables the exploration of complex excitonic phenomena within easily prepared material systems.	Dec 2024
	Heterologous expression, purification and structural features of native Dictyostelium discoideum dye-decolorizing peroxidase bound to a natively incorporated heme Özlem Kalkan , Sravya Kantamneni , Lea Brings , Huijong Han , Richard Bean , Adrian P. Mancuso , Faisal H. M. Koua Frontiers In Chemistry 11 DOI: 10.3389/fchem.2023.1220543 Open Access Show Abstract ▼ Abstract: The Dictyostelium discoideum dye-decolorizing peroxidase (DdDyP) is a newly discovered peroxidase, which belongs to a unique class of heme peroxidase family that lacks homology to the known members of plant peroxidase superfamily. DdDyP catalyzes the H2O2-dependent oxidation of a wide-spectrum of substrates ranging from polycyclic dyes to lignin biomass, holding promise for potential industrial and biotechnological applications. To study the molecular mechanism of DdDyP, highly pure and functional protein with a natively incorporated heme is required, however, obtaining a functional DyP-type peroxidase with a natively bound heme is challenging and often requires addition of expensive biosynthesis precursors. Alternatively, a heme in vitro reconstitution approach followed by a chromatographic purification step to remove the excess heme is often used. Here, we show that expressing the DdDyP peroxidase in ×2 YT enriched medium at low temperature (20°C), without adding heme supplement or biosynthetic precursors, allows for a correct native incorporation of heme into the apo-protein, giving rise to a stable protein with a strong Soret peak at 402 nm. Further, we crystallized and determined the native structure of DdDyP at a resolution of 1.95 Å, which verifies the correct heme binding and its geometry. The structural analysis also reveals a binding of two water molecules at the distal site of heme plane bridging the catalytic residues (Arg239 and Asp149) of the GXXDG motif to the heme-Fe(III) via hydrogen bonds. Our results provide new insights into the geometry of native DdDyP active site and its implication on DyP catalysis.	Aug 2023
	Mix-and-extrude: high-viscosity sample injection towards time-resolved protein crystallography Mohammad Vakili , Huijong Han , Christina Schmidt , Agnieszka Wrona , Marco Kloos , Iñaki De Diego , Katerina Dörner , Tian Geng , Chan Kim , Faisal H. M. Koua , Diogo V. M. Melo , Mathieu Rappas , Adam Round , Ekaterina Round , Marcin Sikorski , Joana Valerio , Tiankun Zhou , Kristina Lorenzen , Joachim Schulz Journal Of Applied Crystallography 56 DOI: 10.1107/S1600576723004405 Open Access Show Abstract ▼ Abstract: Time-resolved crystallography enables the visualization of protein molecular motion during a reaction. Although light is often used to initiate reactions in time-resolved crystallography, only a small number of proteins can be activated by light. However, many biological reactions can be triggered by the interaction between proteins and ligands. The sample delivery method presented here uses a mix-and-extrude approach based on 3D-printed microchannels in conjunction with a micronozzle. The diffusive mixing enables the study of the dynamics of samples in viscous media. The device design allows mixing of the ligands and protein crystals in 2 to 20 s. The device characterization using a model system (fluorescence quenching of iq-mEmerald proteins by copper ions) demonstrated that ligand and protein crystals, each within lipidic cubic phase, can be mixed efficiently. The potential of this approach for time-resolved membrane protein crystallography to support the development of new drugs is discussed.	Aug 2023
	XFEL microcrystallography of self-assembling silver n-alkanethiolates Mariya Aleksich , Daniel W. Paley , Elyse A. Schriber , Will Linthicum , Vanessa Oklejas , David W. Mittan-Moreau , Ryan P. Kelly , Patience A. Kotei , Anita Ghodsi , Raymond G. Sierra , Andrew Aquila , Frédéric Poitevin , Johannes P. Blaschke , Mohammad Vakili , Christopher J. Milne , Fabio Dall’antonia , Dmitry Khakhulin , Fernando Ardana-Lamas , Frederico Lima , Joana Valerio , Huijong Han , Tamires Gallo , Hazem Yousef , Oleksii Turkot , Ivette J. Bermudez Macias , Thomas Kluyver , Philipp Schmidt , Luca Gelisio , Adam R. Round , Yifeng Jiang , Doriana Vinci , Yohei Uemura , Marco Kloos , Mark Hunter , Adrian P. Mancuso , Bryan D. Huey , Lucas R. Parent , Nicholas K. Sauter , Aaron S. Brewster , J. Nathan Hohman Journal Of The American Chemical Society DOI: 10.1021/jacs.3c02183 Show Abstract ▼ Abstract: New synthetic hybrid materials and their increasing complexity have placed growing demands on crystal growth for single-crystal X-ray diffraction analysis. Unfortunately, not all chemical systems are conducive to the isolation of single crystals for traditional characterization. Here, small-molecule serial femtosecond crystallography (smSFX) at atomic resolution (0.833 Å) is employed to characterize microcrystalline silver n-alkanethiolates with various alkyl chain lengths at X-ray free electron laser facilities, resolving long-standing controversies regarding the atomic connectivity and odd–even effects of layer stacking. smSFX provides high-quality crystal structures directly from the powder of the true unknowns, a capability that is particularly useful for systems having notoriously small or defective crystals. We present crystal structures of silver n-butanethiolate (C4), silver n-hexanethiolate (C6), and silver n-nonanethiolate (C9). We show that an odd–even effect originates from the orientation of the terminal methyl group and its role in packing efficiency. We also propose a secondary odd–even effect involving multiple mosaic blocks in the crystals containing even-numbered chains, identified by selected-area electron diffraction measurements. We conclude with a discussion of the merits of the synthetic preparation for the preparation of microdiffraction specimens and compare the long-range order in these crystals to that of self-assembled monolayers.	Jul 2023
	Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease Vasundara Srinivasan , Hévila Brognaro , Prince R. Prabhu , Edmarcia Elisa De Souza , Sebastian Günther , Patrick Y. A. Reinke , Thomas J. Lane , Helen Ginn , Huijong Han , Wiebke Ewert , Janina Sprenger , Faisal H. M. Koua , Sven Falke , Nadine Werner , Hina Andaleeb , Najeeb Ullah , Bruno Alves Franca , Mengying Wang , Angélica Luana C. Barra , Markus Perbandt , Martin Schwinzer , Christina Schmidt , Lea Brings , Kristina Lorenzen , Robin Schubert , Rafael Rahal Guaragna Machado , Erika Donizette Candido , Danielle Bruna Leal Oliveira , Edison Luiz Durigon , Stephan Niebling , Angelica Struve Garcia , Oleksandr Yefanov , Julia Lieske , Luca Gelisio , Martin Domaracky , Philipp Middendorf , Michael Groessler , Fabian Trost , Marina Galchenkova , Aida Rahmani Mashhour , Sofiane Saouane , Johanna Hakanpää , Markus Wolf , Maria Garcia Alai , Dusan Turk , Arwen R. Pearson , Henry N. Chapman , Winfried Hinrichs , Carsten Wrenger , Alke Meents , Christian Betzel Communications Biology 5 DOI: 10.1038/s42003-022-03737-7 Open Access Show Abstract ▼ Abstract: SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host’s innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural compound library. The compounds identified by X-ray screening and complexed to PLpro demonstrate clear inhibition of PLpro in a deISGylation activity assay. Two compounds exhibit distinct antiviral activity in Vero cell line assays and one inhibited a cytopathic effect in non-cytotoxic concentration ranges. In the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.	Aug 2022
	X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease Sebastian Gunther , Patrick Y. A. Reinke , Yaiza Fernández-García , Julia Lieske , Thomas J. Lane , Helen M. Ginn , Faisal H. M. Koua , Christiane Ehrt , Wiebke Ewert , Dominik Oberthuer , Oleksandr Yefanov , Susanne Meier , Kristina Lorenzen , Boris Krichel , Janine-Denise Kopicki , Luca Gelisio , Wolfgang Brehm , Ilona Dunkel , Brandon Seychell , Henry Gieseler , Brenna Norton-Baker , Beatriz Escudero-Pérez , Martin Domaracky , Sofiane Saouane , Alexandra Tolstikova , Thomas A. White , Anna Hänle , Michael Groessler , Holger Fleckenstein , Fabian Trost , Marina Galchenkova , Yaroslav Gevorkov , Chufeng Li , Salah Awel , Ariana Peck , Miriam Barthelmess , Frank Schluenzen , Paulraj Lourdu Xavier , Nadine Werner , Hina Andaleeb , Najeeb Ullah , Sven Falke , Vasundara Srinivasan , Bruno Alves França , Martin Schwinzer , Hévila Brognaro , Cromarte Rogers , Diogo Melo , Joanna J. Zaitseva-Doyle , Juraj Knoska , Gisel E. Peña-Murillo , Aida Rahmani Mashhour , Vincent Hennicke , Pontus Fischer , Johanna Hakanpää , Jan Meyer , Philip Gribbon , Bernhard Ellinger , Maria Kuzikov , Markus Wolf , Andrea R. Beccari , Gleb Bourenkov , David Von Stetten , Guillaume Pompidor , Isabel Bento , Saravanan Panneerselvam , Ivars Karpics , Thomas R. Schneider , Maria Marta Garcia-Alai , Stephan Niebling , Christian Günther , Christina Schmidt , Robin Schubert , Huijong Han , Juliane Boger , Diana C. F. Monteiro , Linlin Zhang , Xinyuanyuan Sun , Jonathan Pletzer-Zelgert , Jan Wollenhaupt , Christian G. Feiler , Manfred S. Weiss , Eike-Christian Schulz , Pedram Mehrabi , Katarina Karničar , Aleksandra Usenik , Jure Loboda , Henning Tidow , Ashwin Chari , Rolf Hilgenfeld , Charlotte Uetrecht , Russell Cox , Andrea Zaliani , Tobias Beck , Matthias Rarey , Stephan Günther , Dusan Turk , Winfried Hinrichs , Henry N. Chapman , Arwen R. Pearson , Christian Betzel , Alke Meents Science DOI: 10.1126/science.abf7945 Open Access Show Abstract ▼ Abstract: The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.	Apr 2021
I04-1-Macromolecular Crystallography (fixed wavelength) I24-Microfocus Macromolecular Crystallography	Atomic view into Plasmodium actin polymerization, ATP hydrolysis, and fragmentation Esa-Pekka Kumpula , Andrea J. Lopez , Leila Tajedin , Huijong Han , Inari Kursula Plos Biology DOI: 10.1371/journal.pbio.3000315 Open Access Show Abstract ▼ Abstract: Plasmodium actins form very short filaments and have a noncanonical link between ATP hydrolysis and polymerization. Long filaments are detrimental to the parasites, but the structural factors constraining Plasmodium microfilament lengths have remained unknown. Using high-resolution crystallography, we show that magnesium binding causes a slight flattening of the Plasmodium actin I monomer, and subsequent phosphate release results in a more twisted conformation. Thus, the Mg-bound monomer is closer in conformation to filamentous (F) actin than the Ca form, and this likely facilitates polymerization. A coordinated potassium ion resides in the active site during hydrolysis and leaves together with the phosphate, a process governed by the position of the Arg178/Asp180-containing A loop. Asp180 interacts with either Lys270 or His74, depending on the protonation state of the histidine, while Arg178 links the inner and outer domains (ID and OD) of the actin protomer. Hence, the A loop acts as a switch between stable and unstable filament conformations, the latter leading to fragmentation. Our data provide a comprehensive model for polymerization, ATP hydrolysis and phosphate release, and fragmentation of parasite microfilaments. Similar mechanisms may well exist in canonical actins, although fragmentation is much less favorable due to several subtle sequence differences as well as the methylation of His73, which is absent on the corresponding His74 in Plasmodium actin I.	Jun 2019

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User