IUCrJ最新文献

{"title":"The evolution of raw data archiving and the growth of its importance in crystallography","authors":"John R. Helliwell ,&nbsp;James R. Hester ,&nbsp;Loes M. J. Kroon-Batenburg ,&nbsp;Brian McMahon ,&nbsp;Selina L. S. Storm ,&nbsp;P. Lightfoot (Editor)","doi":"10.1107/S205225252400455X","DOIUrl":"10.1107/S205225252400455X","url":null,"abstract":"<div><p>The IUCr 75th Congress in Melbourne hosted a workshop on raw data reuse, continuing efforts to promote discussions and plans within crystallography, diffraction and scattering communities. These initiatives build on earlier IUCr funded workshops, aiming to establish ground truth obtained from research results through raw data archiving potential.</p></div><div><p>The hardware for data archiving has expanded capacities for digital storage enormously in the past decade or more. The IUCr evaluated the costs and benefits of this within an official working group which advised that raw data archiving would allow ground truth reproducibility in published studies. Consultations of the IUCr’s Commissions ensued via a newly constituted standing advisory committee, the Committee on Data. At all stages, the IUCr financed workshops to facilitate community discussions and possible methods of raw data archiving implementation. The recent launch of the <em>IUCrData</em> journal’s <em>Raw Data Letters</em> is a milestone in the implementation of raw data archiving beyond the currently published studies: it includes diffraction patterns that have not been fully interpreted, if at all. The IUCr 75th Congress in Melbourne included a workshop on raw data reuse, discussing the successes and ongoing challenges of raw data reuse. This article charts the efforts of the IUCr to facilitate discussions and plans relating to raw data archiving and reuse within the various communities of crystallography, diffraction and scattering.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 4","pages":"Pages 464-475"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the microscopic divide: a comprehensive overview of micro-crystallization and in vivo crystallography","authors":"Leonard Michel Gabriel Chavas ,&nbsp;Fasséli Coulibaly ,&nbsp;Damià Garriga ,&nbsp;E. N. Baker (Editor)","doi":"10.1107/S205225252400513X","DOIUrl":"10.1107/S205225252400513X","url":null,"abstract":"<div><p>The 26th IUCr congress held in Melbourne brought discussions on micro-crystallization and <em>in vivo</em> crystallography within structural biology to the forefront, highlighting innovative approaches and collaborative efforts to advance macromolecular research.</p></div><div><p>A series of events underscoring the significant advancements in micro-crystallization and <em>in vivo</em> crystallography were held during the 26th IUCr Congress in Melbourne, positioning microcrystallography as a pivotal field within structural biology. Through collaborative discussions and the sharing of innovative methodologies, these sessions outlined frontier approaches in macromolecular crystallography. This review provides an overview of this rapidly moving field in light of the rich dialogues and forward-thinking proposals explored during the congress workshop and microsymposium. These advances in microcrystallography shed light on the potential to reshape current research paradigms and enhance our comprehension of biological mechanisms at the molecular scale.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 4","pages":"Pages 476-485"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystallographic phase identifier of a convolutional self-attention neural network (CPICANN) on powder diffraction patterns","authors":"Shouyang Zhang ,&nbsp;Bin Cao ,&nbsp;Tianhao Su ,&nbsp;Yue Wu ,&nbsp;Zhenjie Feng ,&nbsp;Jie Xiong ,&nbsp;Tong-Yi Zhang ,&nbsp;A. Fitch (Editor)","doi":"10.1107/S2052252524005323","DOIUrl":"10.1107/S2052252524005323","url":null,"abstract":"<div><p>The development of CPICANN, a novel convolutional self-attention neural network, represents a groundbreaking approach in materials informatics. By leveraging the convolutional self-attention mechanism, CPICANN automates and significantly enhances the efficiency of crystal phase identification from whole X-ray powder diffraction patterns, marking a substantial advancement over traditional time-consuming methods.</p></div><div><p>Spectroscopic data, particularly diffraction data, are essential for materials characterization due to their comprehensive crystallographic information. The current crystallographic phase identification, however, is very time consuming. To address this challenge, we have developed a real-time crystallographic phase identifier based on a convolutional self-attention neural network (CPICANN). Trained on 692 190 simulated powder X-ray diffraction (XRD) patterns from 23 073 distinct inorganic crystallographic information files, CPICANN demonstrates superior phase-identification power. Single-phase identification on simulated XRD patterns yields 98.5 and 87.5% accuracies with and without elemental information, respectively, outperforming <em>JADE</em> software (68.2 and 38.7%, respectively). Bi-phase identification on simulated XRD patterns achieves 84.2 and 51.5% accuracies, respectively. In experimental settings, CPICANN achieves an 80% identification accuracy, surpassing <em>JADE</em> software (61%). Integration of CPICANN into XRD refinement software will significantly advance the cutting-edge technology in XRD materials characterization.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 4","pages":"Pages 634-642"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of COF-300 synthesis: probing degradation processes and 3D electron diffraction structure","authors":"Laurens Bourda ,&nbsp;Subhrajyoti Bhandary ,&nbsp;Sho Ito ,&nbsp;Christian R. Göb ,&nbsp;Pascal Van Der Voort ,&nbsp;Kristof Van Hecke ,&nbsp;L. Meshi (Editor)","doi":"10.1107/S2052252524003713","DOIUrl":"10.1107/S2052252524003713","url":null,"abstract":"<div><p>Detailed analysis of the influence of time and temperature on the synthesis of COF-300 showed partial linker degradation but still allowed 3D electron diffraction structure solution using optimized conditions.</p></div><div><p>Although COF-300 is often used as an example to study the synthesis and structure of (3D) covalent organic frameworks (COFs), knowledge of the underlying synthetic processes is still fragmented. Here, an optimized synthetic procedure based on a combination of linker protection and modulation was applied. Using this approach, the influence of time and temperature on the synthesis of COF-300 was studied. Synthesis times that were too short produced materials with limited crystallinity and porosity, lacking the typical pore flexibility associated with COF-300. On the other hand, synthesis times that were too long could be characterized by loss of crystallinity and pore order by degradation of the tetrakis(4-aminophenyl)methane (TAM) linker used. The presence of the degradation product was confirmed by visual inspection, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). As TAM is by far the most popular linker for the synthesis of 3D COFs, this degradation process might be one of the reasons why the development of 3D COFs is still lagging compared with 2D COFs. However, COF crystals obtained via an optimized procedure could be structurally probed using 3D electron diffraction (3DED). The 3DED analysis resulted in a full structure determination of COF-300 at atomic resolution with satisfying data parameters. Comparison of our 3DED-derived structural model with previously reported single-crystal X-ray diffraction data for this material, as well as parameters derived from the Cambridge Structural Database, demonstrates the high accuracy of the 3DED method for structure determination. This validation might accelerate the exploitation of 3DED as a structure determination technique for COFs and other porous materials.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 4","pages":"Pages 510-518"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of definitions in crystallography","authors":"Olga Anosova ,&nbsp;Vitaliy Kurlin ,&nbsp;Marjorie Senechal ,&nbsp;D. Gratias (Editor)","doi":"10.1107/S2052252524004056","DOIUrl":"10.1107/S2052252524004056","url":null,"abstract":"<div><p>This paper proposes a rigorous definition of a periodic structure as an equivalence class of periodic sets under rigid motion, which is a composition of translations and rotations.</p></div><div><p>This paper was motivated by the articles ‘Same or different – that is the question’ in <em>CrystEngComm</em> (July 2020) and ‘Change to the definition of a crystal’ in the <em>IUCr Newsletter</em> (June 2021). Experimental approaches to crystal comparisons require rigorously defined classifications in crystallography and beyond. Since crystal structures are determined in a rigid form, their strongest equivalence in practice is rigid motion, which is a composition of translations and rotations in 3D space. Conventional representations based on reduced cells and standardizations theoretically distinguish all periodic crystals. However, all cell-based representations are inherently discontinuous under almost any atomic displacement that can arbitrarily scale up a reduced cell. Hence, comparison of millions of known structures in materials databases requires continuous distance metrics.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 4","pages":"Pages 453-463"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scanning WAXS microscopy of regenerated cellulose fibers at mesoscopic resolution","authors":"Sara Johansson ,&nbsp;Francesco Scattarella ,&nbsp;Sebastian Kalbfleisch ,&nbsp;Ulf Johansson ,&nbsp;Christopher Ward ,&nbsp;Crispin Hetherington ,&nbsp;Herbert Sixta ,&nbsp;Stephen Hall ,&nbsp;Cinzia Giannini ,&nbsp;Ulf Olsson ,&nbsp;M. Takata (Editor)","doi":"10.1107/S205225252400383X","DOIUrl":"10.1107/S205225252400383X","url":null,"abstract":"<div><p>Scanning WAXS microscopy of a regenerated cellulose textile fiber reveals a radial gradient in the degree of orientation of the crystallite.</p></div><div><p>In this work, regenerated cellulose textile fibers, Ioncell-F, dry-wet spun with different draw ratios, have been investigated by scanning wide-angle X-ray scattering (WAXS) using a mesoscopic X-ray beam. The fibers were found to be homogeneous on the 500 nm length scale. Analysis of the azimuthal angular dependence of a crystalline Bragg spot intensity revealed a radial dependence of the degree of orientation of crystallites that was found to increase with the distance from the center of the fiber. We attribute this to radial velocity gradients during the extrusion of the spin dope and the early stage of drawing. On the other hand, the fiber crystallinity was found to be essentially homogeneous over the fiber cross section.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 4","pages":"Pages 570-577"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanostructure and dynamics of N-truncated copper amyloid-β peptides from advanced X-ray absorption fine structure","authors":"Ruwini S. K. Ekanayake ,&nbsp;Victor A. Streltsov ,&nbsp;Stephen P. Best ,&nbsp;Christopher T. Chantler ,&nbsp;V. K. Peterson (Editor)","doi":"10.1107/S2052252524001830","DOIUrl":"10.1107/S2052252524001830","url":null,"abstract":"<div><p>An X-ray absorption spectroscopy electrochemical cell was used to collect high-quality X-ray absorption spectroscopy measurements of N-truncated Cu:amyloid-β (Cu:Aβ) samples under near-physiological conditions. The geometry of binding sites for the copper binding in Aβ_4–8/12/16 and the ability of these peptides to perform redox cycles in a manner that might produce toxicity in human brains were determined.</p></div><div><p>An X-ray absorption spectroscopy (XAS) electrochemical cell was used to collect high-quality XAS measurements of N-truncated Cu:amyloid-β (Cu:Aβ) samples under near-physiological conditions. N-truncated Cu:Aβ peptide complexes contribute to oxidative stress and neurotoxicity in Alzheimer’s patients’ brains. However, the redox properties of copper in different Aβ peptide sequences are inconsistent. Therefore, the geometry of binding sites for the copper binding in Aβ_4–8/12/16 was determined using novel advanced extended X-ray absorption fine structure (EXAFS) analysis. This enables these peptides to perform redox cycles in a manner that might produce toxicity in human brains. Fluorescence XAS measurements were corrected for systematic errors including defective-pixel data, monochromator glitches and dispersion of pixel spectra. Experimental uncertainties at each data point were measured explicitly from the point-wise variance of corrected pixel measurements. The copper-binding environments of Aβ_4–8/12/16 were precisely determined by fitting XAS measurements with propagated experimental uncertainties, advanced analysis and hypothesis testing, providing a mechanism to pursue many similarly complex questions in bioscience. The low-temperature XAS measurements here determine that Cu^II is bound to the first amino acids in the high-affinity amino-terminal copper and nickel (ATCUN) binding motif with an oxygen in a tetragonal pyramid geometry in the Aβ_4–8/12/16 peptides. Room-temperature XAS electrochemical-cell measurements observe metal reduction in the Aβ_4–16 peptide. Robust investigations of XAS provide structural details of Cu^II binding with a very different <em>bis</em>-His motif and a water oxygen in a quasi-tetrahedral geometry. Oxidized XAS measurements of Aβ_4–12/16 imply that both Cu^II and Cu^III are accommodated in an ATCUN-like binding site. Hypotheses for these Cu^I, Cu^II and Cu^III geometries were proven and disproven using the novel data and statistical analysis including <em>F</em> tests. Structural parameters were determined with an accuracy some tenfold better than literature claims of past work. A new protocol was also developed using EXAFS data analysis for monitoring radiation damage. This gives a template for advanced analysis of complex biosystems.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 3","pages":"Pages 325-346"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140716153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RCSB Protein Data Bank: supporting research and education worldwide through explorations of experimentally determined and computationally predicted atomic level 3D biostructures","authors":"Stephen K. Burley ,&nbsp;Dennis W. Piehl ,&nbsp;Brinda Vallat ,&nbsp;Christine Zardecki ,&nbsp;E. N. Baker (Editor)","doi":"10.1107/S2052252524002604","DOIUrl":"10.1107/S2052252524002604","url":null,"abstract":"<div><p>The RCSB PDB research-focused web portal at <span>https://www.rcsb.org/</span> provides important tools and resources to search, visualize and analyze experimentally determined 3D biostructures alongside computed structure models of proteins predicted using artificial intelligence/machine-learning based tools.</p></div><div><p>The Protein Data Bank (PDB) was established as the first open-access digital data resource in biology and medicine in 1971 with seven X-ray crystal structures of proteins. Today, the PDB houses &gt;210 000 experimentally determined, atomic level, 3D structures of proteins and nucleic acids as well as their complexes with one another and small molecules (<em>e.g.</em> approved drugs, enzyme cofactors). These data provide insights into fundamental biology, biomedicine, bioenergy and biotechnology. They proved particularly important for understanding the SARS-CoV-2 global pandemic. The US-funded Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) and other members of the Worldwide Protein Data Bank (wwPDB) partnership jointly manage the PDB archive and support &gt;60 000 ‘data depositors’ (structural biologists) around the world. wwPDB ensures the quality and integrity of the data in the ever-expanding PDB archive and supports global open access without limitations on data usage. The RCSB PDB research-focused web portal at <span>https://www.rcsb.org/</span> (RCSB.org) supports millions of users worldwide, representing a broad range of expertise and interests. In addition to retrieving 3D structure data, PDB ‘data consumers’ access comparative data and external annotations, such as information about disease-causing point mutations and genetic variations. RCSB.org also provides access to &gt;1 000 000 computed structure models (CSMs) generated using artificial intelligence/machine-learning methods. To avoid doubt, the provenance and reliability of experimentally determined PDB structures and CSMs are identified. Related training materials are available to support users in their RCSB.org explorations.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 3","pages":"Pages 279-286"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140717229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamical refinement with multipolar electron scattering factors","authors":"Barbara Olech ,&nbsp;Petr Brázda ,&nbsp;Lukas Palatinus ,&nbsp;Paulina Maria Dominiak ,&nbsp;M. Gemmi (Editor)","doi":"10.1107/S2052252524001763","DOIUrl":"10.1107/S2052252524001763","url":null,"abstract":"<div><p>Transferable aspherical atom model dynamical refinement on precession electron diffraction data for 1-methyl­uracil crystals offers superior performance compared with the independent atom model and reveals that the quality of 3D electron diffraction data and dynamical refinement is already sufficient to detect minute variations of the electrostatic potential caused by bonding and intermolecular interactions.</p></div><div><p>Dynamical refinement is a well established method for refining crystal structures against 3D electron diffraction (ED) data and its benefits have been discussed in the literature [Palatinus, Petříček &amp; Corrêa, (2015). <em>Acta Cryst.</em> A<strong>71</strong>, 235–244; Palatinus, Corrêa <em>et al.</em> (2015). <em>Acta Cryst.</em> B<strong>71</strong>, 740–751]. However, until now, dynamical refinements have only been conducted using the independent atom model (IAM). Recent research has shown that a more accurate description can be achieved by applying the transferable aspherical atom model (TAAM), but this has been limited only to kinematical refinements [Gruza <em>et al.</em> (2020). <em>Acta Cryst.</em> A<strong>76</strong>, 92–109; Jha <em>et al.</em> (2021). <em>J. Appl. Cryst.</em> <strong>54</strong>, 1234–1243]. In this study, we combine dynamical refinement with TAAM for the crystal structure of 1-methyl­uracil, using data from precession ED. Our results show that this approach improves the residual Fourier electrostatic potential and refinement figures of merit. Furthermore, it leads to systematic changes in the atomic displacement parameters of all atoms and the positions of hydrogen atoms. We found that the refinement results are sensitive to the parameters used in the TAAM modelling process. Though our results show that TAAM offers superior performance compared with IAM in all cases, they also show that TAAM parameters obtained by periodic DFT calculations on the refined structure are superior to the TAAM parameters from the UBDB/MATTS database. It appears that multipolar parameters transferred from the database may not be sufficiently accurate to provide a satisfactory description of all details of the electrostatic potential probed by the 3D ED experiment.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 3","pages":"Pages 309-324"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11067749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biophysical and structural study of La Crosse virus endonuclease inhibition for the development of new antiviral options","authors":"Mikael Feracci ,&nbsp;Sergio Hernandez ,&nbsp;Laura Garlatti ,&nbsp;Clemence Mondielli ,&nbsp;Renaud Vincentelli ,&nbsp;Bruno Canard ,&nbsp;Juan Reguera ,&nbsp;François Ferron ,&nbsp;Karine Alvarez ,&nbsp;Z.-J. Liu (Editor)","doi":"10.1107/S205225252400304X","DOIUrl":"10.1107/S205225252400304X","url":null,"abstract":"<div><p>A structural analysis of several metal-ion binders that inhibit viral endonucleases is performed.</p></div><div><p>The large <em>Bunyavirales</em> order includes several families of viruses with a segmented ambisense (−) RNA genome and a cytoplasmic life cycle that starts by synthesizing viral mRNA. The initiation of transcription, which is common to all members, relies on an endonuclease activity that is responsible for cap-snatching. In La Crosse virus, an orthobunyavirus, it has previously been shown that the cap-snatching endonuclease resides in the N-terminal domain of the L protein. Orthobunyaviruses are transmitted by arthropods and cause diseases in cattle. However, California encephalitis virus, La Crosse virus and Jamestown Canyon virus are North American species that can cause encephalitis in humans. No vaccines or antiviral drugs are available. In this study, three known Influenza virus endonuclease inhibitors (DPBA, L-742,001 and baloxavir) were repurposed on the La Crosse virus endonuclease. Their inhibition was evaluated by fluorescence resonance energy transfer and their mode of binding was then assessed by differential scanning fluorimetry and microscale thermophoresis. Finally, two crystallographic structures were obtained in complex with L-742,001 and baloxavir, providing access to the structural determinants of inhibition and offering key information for the further development of <em>Bunyavirales</em> endonuclease inhibitors.</p></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"11 3","pages":"Pages 374-383"},"PeriodicalIF":3.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}