I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[39189]
Open Access
Abstract: The enzymes Cannabichromenic Acid Synthase (CBCAS), Cannabidiolic Acid Synthase (CBDAS) and Tetrahydrocannabinolic Acid Synthase (THCAS) are together the major cannabinoid synthase enzymes responsible for the biosynthesis of their respective metabolites from a common precursor Cannabigerolic Acid (CBGA). As the catalysts responsible for generating biological molecules of significant pharmaceutical value, there has been considerable interest in the enzymes with respect to heterologous production, mechanism, and incorporation into synthetic biology pathways for the facile industrial production of these molecules. The enzymes share high degrees of homology, and therefore their distinct specificities are governed by very subtle differences in sequence and therefore structure, although, until now, only a structure for THCAS has been reported. In this report, we present structures of CBCAS, CBDAS and a structure of THCAS at a higher resolution than the known structure, each in complex with their flavin coenzyme FAD. The structures reveal active site differences that may be responsible for the complementary activities observed, in terms of both first-shell amino acid substitutions, but also in more remote residues that influence active site topology through referred effects, or that have effects on substrate access. The structures provide a useful and informative platform for the rational engineering of improved or altered chemoselectivity in these enzymes.
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Dec 2026
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Detectors
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N.
Goyal
,
F. J.
Iguaz
,
S.
Aplin
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A.
Balerna
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P.
Bell
,
J.
Casas
,
M.
Cascella
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S.
Chatterji
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C.
Cohen
,
E.
Collet
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E N.
Gimenez
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H.
Graafsma
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H.
Hirsemann
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K.
Klementiev
,
T.
Kolodziej
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T.
Martin
,
Ralf H.
Menk
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C.
Menneglier
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C.
Meraihia
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J. R.
Murias
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M.
Porro
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M.
Quispe
,
B.
Schmitt
,
S.
Scully
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M.
Turcato
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C.
Ward
,
E.
Welter
Open Access
Abstract: The first operational prototype of a high-purity germanium (HPGe) detector developed within the European LEAPS-INNOV project is presented in this work. This prototype features a monolithic, multi-element sensor optimized for high-resolution X-ray spectroscopy in the hard X-ray regime, intended for handing high count rates of 30 Mcps, across a broad energy range (5–100 keV). The present prototype demonstrates a throughput of about 150–200 kcps/pixel, corresponding to a total count rate of about 1.5–2 Mcps for the full 10 element detector. We discuss here a complete laboratory-based characterization of the detector’s performance, as well as an on-beam evaluation at the BM05 beamline of the ESRF synchrotron facility, using monochromatic X-rays in the 20–50 keV energy range. We provide a detailed performance assessment that also includes a phenomenological defect-depth estimation model.
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Dec 2026
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I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[34182]
Open Access
Abstract: Chikungunya virus (CHIKV) outbreaks impose significant burdens on healthcare systems and raise an urgent need for effective antiviral therapies. So far there are no specific drugs against CHIKV infection. CHIKV-encoded macrodomain is critical for virulence and counteracts the host immune response, representing a promising antiviral drug target. Here, we describe small molecule inhibitors targeting the CHIKV macrodomain. Compound 1 (MDOLL-0273) was identified through a high-throughput screening using a fluorescence resonance energy transfer based assay, exhibiting an IC50 of 8.9 μM, and its inhibitory activity was validated through multiple orthogonal assays. The compound features a thiobarbiturate-indole scaffold and shows high selectivity over a panel of human and viral ADP-ribose binding and hydrolyzing proteins. X-ray crystallography revealed that the inhibitor occupies an adenine binding site of the macrodomain and extends into a novel cryptic pocket. Guided by structure-activity relationship studies, compound 11 (MDOLL-0591) of the developed series with similar IC50 of 10 μM but with increased lipophilicity was discovered to have antiviral activity against CHIKV in cell culture, demonstrating that macrodomain could be targeted in virus infections.
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Nov 2026
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B18-Core EXAFS
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Diamond Proposal Number(s):
[34632]
Open Access
Abstract: Carbon dioxide (CO2) hydrogenation represents a central route for sustainable fuel production and carbon recycling, yet its efficiency is critically dependent on the structural and electronic properties of the catalyst. In practical heterogeneous systems prepared by conventional wet-chemical methods, a distribution of active sites, ranging from atomically dispersed species to subnanometric clusters and nanoparticles, typically coexist in the final catalyst. Here, we investigate how support defect engineering governs this distribution in Ru/TiO2 catalysts with varying metal loadings and oxidative pre-treatments. Comprehensive spectroscopic and imaging analyses, including XPS, HR-STEM, and XAS established a clear correlation between Ru structure and catalytic behavior. Critically low Ru loadings (0.2 wt%) induced a transition from metallic nanoparticles to highly dispersed and single atom species, while oxidative pretreatment generated RuO2 like domains. A fraction of isolated Ru atoms persisted, particularly on defect-rich TiO2, where oxygen vacancies act as anchoring sites, improving stability under redox conditions. Catalytic testing revealed that Ru dispersion and oxidation state jointly determine activity and selectivity: extended metallic Ru or oxidized Ru nanoparticles favor complete hydrogenation to CH4, whereas isolated Ru species promote CO formation via the reverse water–gas shift pathway. The coexistence of these Ru configurations is associated with enhanced low temperature activity, while defect engineered supports improve stability against deactivation. Defect engineering of TiO2 provides an effective strategy to stabilize atomically dispersed Ru and to balance nanoparticles and atomic species, offering a versatile strategy to tune CO2 hydrogenation performance and advance the design of Ru based catalysts for sustainable hydrogenation processes.
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Nov 2026
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B18-Core EXAFS
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Diamond Proposal Number(s):
[33047]
Open Access
Abstract: Human skeletal samples burned between 200 and 1000 °C, in both aerobic and anaerobic conditions, were probed by synchrotron-based Extended X-ray Absorption Fine Structure with a view to interpret heat-induced variations in chemical composition and structure. Heat-prompted changes in Ca2+ first and second coordination shells were unveiled (regarding PO43−, CO32− and/or OH− ligands). A higher crystallinity degree was found for 800-1000 °C burning temperatures as compared to 200-700 °C, in agreement with the higher amount of organic components in moderately heated samples. The unique local structural information delivered by XAS, particularly on the Ca2+ coordination environment which determines bone's structural features and degree of crystallinity, enabled an improved understanding of the heat-elicited changes undergone by bone, not previously accessed by other techniques. This is an innovative study, with a high impact in forensic and bioarchaeological research, focused on the analysis of burned human skeletal remains.
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Oct 2026
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Open Access
Abstract: Bonkowski and De Souza [Sol. Stat. Ionics 429, 116967 (2025)] provide a guide for performing molecular dynamics simulations of ion transport, including methods for estimating diffusion coefficients and their uncertainties from mean-squared displacement (MSD) data. The discussion of uncertainty in estimated diffusion coefficients presents the statistical properties of specific analysis protocols—ordinary least squares regression with particular data processing choices and other, statistically equivalent, approaches—without explicitly stating the scope of applicability for these results. Without explicit scope statements, the guide presents these results as universal characteristics of diffusion coefficient estimation; i.e., uncertainty in is determined only by the input simulation data. Here, we clarify that for diffusion coefficients estimated by linear regression of MSD data, the uncertainty depends not only on the input simulation data, but also on the choice of statistical estimator (OLS, WLS, GLS) and data processing decisions (fitting window extent, time-averaging). By clarifying this dependence on analysis protocol, we hope to help researchers avoid incorrect uncertainty estimates and encourage the adoption of statistically efficient methods for analysing molecular dynamics simulations.
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Oct 2026
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I04-Macromolecular Crystallography
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Open Access
Abstract: Motivated by the need for a convenient way to demonstrate the growth of crystals in glass plates by the lipid cubic phase method at crystallization workshops and courses, we developed a lightweight, portable, compact and inexpensive digital microscope device. The device is built around hand-held Wi-Fi and hardwired digital microscopes that are available commercially at low cost and that can use cell phones and personal computers for imaging without the need for unwieldy eyepieces. The device provides illumination from above and below the crystallization plate over a range of brightness levels. It can be used with regular white light and with polarized light to detect birefringent crystals. While not the focus of this study, the new device has been shown to also work with batch and vapour-diffusion plates. Remote monitoring of crystallization plates in a cold cabinet or walk-in refrigerator at 4 °C is possible with the Wi-Fi microscope. Crystals grown in lipid cubic phase and vapour-diffusion crystallization plates were harvested with the aid of the new device and used for diffraction data collection, leading to structure determination at high resolution. Most parts of the device were 3D printed in polylactic acid plastic. The corresponding STL files, included as part of this publication, can be used to make replicates of the current microscope and to produce bespoke devices suited to the specific needs of the user. We envision using the new device for outreach activities at primary, secondary and third-level schools, and at science fairs in support of the citizen scientist. Relatedly, in this study examples are included of recorded images of plant and animal tissue sections. One reveals birefringent materials in a tomato leaf. Another shows optically active crystals of calcium oxalate in onion tunic tissue.
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Oct 2026
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B18-Core EXAFS
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Diamond Proposal Number(s):
[39526]
Open Access
Abstract: There is increasing interest in using Fe-rich materials in cement, yet the Fe speciation in hydrated cement paste remains poorly understood. This study quantitatively investigates the fate of amorphous Fe in hydrated white Portland cement-fayalitic slag pastes with varying Fe contents cured for 3, 28, and 90 days. The results show that Fe precipitated as ferrihydrite and potentially adsorbed on calcium (alumino)silicate hydrate (C-(A)-S-H) after 3 days of hydration. Afterwards, Fe stabilised in Fe-siliceous hydrogarnet and Fe-adsorbed C-(A)-S-H phases, accounting for ∼15% and ∼ 85% of total reacted Fe, respectively, after hydration for 90 days. The high Fe uptake by C-(A)-S-H was mainly attributed to Fe(III) adsorption rather than Fe(II). Thermodynamic modelling combined with microstructural analysis supported the predominant distribution of Fe on the C-(A)-S-H phase. These findings can advance understanding in using reactive Fe-containing materials in Portland cement pastes and the development of their chemical and physical properties.
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Oct 2026
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Open Access
Abstract: Non-destructive evaluation (NDE) is used to detect and characterise defects in safety-critical components. This paper focuses on manual pulse-echo ultrasonic testing applied to the sizing of surface-breaking crack-like defects. In the field, practitioners often use A-scans from single element, pulse-echo ultrasonic testing. Machine learning, and in particular neural networks, have huge potential for applications to NDE-type problems due to their ability to recognise patterns from signals. Accurate predictions require large, labelled databases yet there is a paucity of such ultrasonic data for surface-breaking thermally fatigued cracks. To address this deficit, this work demonstrates that a database composed entirely of simulated, synthetic A-scans provides promising predictions on measured data. Crack height predictions with a mean absolute error of around 0.124 mm are achieved for measured data (on cracks between 0.5 mm and 4 mm). When tested on simulated A-scans, both height and tilt angle predictions are extremely accurate (to within 0.035 mm and 0.41°, respectively). To achieve such accuracy the in-situ inspection techniques were mimicked, with particular attention paid to the characteristics of the thermally fatigued crack species, and the single element transducer and its input signal. The details of the finite element simulations that generated the database are presented here. The work outlined in this paper shows that A-scans can be used to size defects using neural networks trained entirely on synthetic data, informed by experimental measurements, with potential applications for improving the efficiency of sizing cracks in-situ.
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Oct 2026
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I04-Macromolecular Crystallography
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Stéphane
Bourg
,
Matthieu
Place
,
Chloé
Copin
,
Apirat
Chaikuad
,
Thomas
Robert
,
Hanna
Holzmann
,
Susanne
Müller
,
Stéphane
Bach
,
Sandrine
Ruchaud
,
Stefan
Knapp
,
Frédéric
Buron
,
Sylvain
Routier
,
Pascal
Bonnet
Open Access
Abstract: CLK1 is one of the four human isoforms of the cdc2-like (CLK) kinases that has been suggested as a therapeutic target in diverse diseases based on its important role regulating mRNA splicing. For example, CLKs and closely related kinases such as DYRK1A have been targeted in Alzheimer’s disease and other diseases in which splice site selection contributes to the disease development. Here we have developed an efficient in silico fragment-based ligand design approach to identify novel CLK1 inhibitors with excellent ligand efficiency based on an imidazo[2,1-b][1,3,4]thiadiazole fragment. More than one million docking poses were generated from 26,225 unique virtual compounds, and after applying several filtering steps, 11 compounds were selected, synthesized and their CLK1 inhibition and cellular potency were evaluated. Gratifyingly, inhibitor potencies were in excellent agreement with predicted values and crystallographic data of an inhibitor bound to CLK1 confirmed the unusual binding mode of the compounds.
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Oct 2026
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