Acta Crystallographica. Section D, Structural Biology最新文献_第2页

Elucidating polymorphs of crystal structures by intensity-based hierarchical clustering analysis of multiple diffraction data sets. 通过多个衍射数据集的基于强度的层次聚类分析来阐明晶体结构的多晶型。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-10-01 Epub Date: 2023-10-25 DOI: 10.1107/S2059798323007039

Hiroaki Matsuura, Naoki Sakai, Sachiko Toma-Fukai, Norifumi Muraki, Koki Hayama, Hironari Kamikubo, Shigetoshi Aono, Yoshiaki Kawano, Masaki Yamamoto, Kunio Hirata

{"title":"Elucidating polymorphs of crystal structures by intensity-based hierarchical clustering analysis of multiple diffraction data sets.","authors":"Hiroaki Matsuura, Naoki Sakai, Sachiko Toma-Fukai, Norifumi Muraki, Koki Hayama, Hironari Kamikubo, Shigetoshi Aono, Yoshiaki Kawano, Masaki Yamamoto, Kunio Hirata","doi":"10.1107/S2059798323007039","DOIUrl":"10.1107/S2059798323007039","url":null,"abstract":"In macromolecular structure determination using X-ray diffraction from multiple crystals, the presence of different structures (structural polymorphs) necessitates the classification of the diffraction data for appropriate structural analysis. Hierarchical clustering analysis (HCA) is a promising technique that has so far been used to extract isomorphous data, mainly for single-structure determination. Although in principle the use of HCA can be extended to detect polymorphs, the absence of a reference to define the threshold used to group the isomorphous data sets (the `isomorphic threshold') poses a challenge. Here, unit-cell-based and intensity-based HCAs have been applied to data sets for apo trypsin and inhibitor-bound trypsin that were mixed post data acquisition to investigate the efficacy of HCA in classifying polymorphous data sets. Single-step intensity-based HCA successfully classified polymorphs with a certain `isomorphic threshold'. In data sets for several samples containing an unknown degree of structural heterogeneity, polymorphs could be identified by intensity-based HCA using the suggested `isomorphic threshold'. Polymorphs were also detected in single crystals using data collected using the continuous helical scheme. These findings are expected to facilitate the determination of multiple structural snapshots by exploiting automated data collection and analysis.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":"79 Pt 10","pages":"909-924"},"PeriodicalIF":2.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10565733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41187822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A user-friendly plug-and-play cyclic olefin copolymer-based microfluidic chip for room-temperature, fixed-target serial crystallography. 一种用户友好的即插即用的基于环烯烃共聚物的微流控芯片，用于室温、固定靶序列晶体学。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-10-01 Epub Date: 2023-09-25 DOI: 10.1107/S2059798323007027

Zhongrui Liu, Kevin K Gu, Megan L Shelby, Deepshika Gilbile, Artem Y Lyubimov, Silvia Russi, Aina E Cohen, Sankar Raju Narayanasamy, Sabine Botha, Christopher Kupitz, Raymond G Sierra, Fredric Poitevin, Antonio Gilardi, Stella Lisova, Matthew A Coleman, Matthias Frank, Tonya L Kuhl

{"title":"A user-friendly plug-and-play cyclic olefin copolymer-based microfluidic chip for room-temperature, fixed-target serial crystallography.","authors":"Zhongrui Liu, Kevin K Gu, Megan L Shelby, Deepshika Gilbile, Artem Y Lyubimov, Silvia Russi, Aina E Cohen, Sankar Raju Narayanasamy, Sabine Botha, Christopher Kupitz, Raymond G Sierra, Fredric Poitevin, Antonio Gilardi, Stella Lisova, Matthew A Coleman, Matthias Frank, Tonya L Kuhl","doi":"10.1107/S2059798323007027","DOIUrl":"10.1107/S2059798323007027","url":null,"abstract":"Over the past two decades, serial X-ray crystallography has enabled the structure determination of a wide range of proteins. With the advent of X-ray free-electron lasers (XFELs), ever-smaller crystals have yielded high-resolution diffraction and structure determination. A crucial need to continue advancement is the efficient delivery of fragile and micrometre-sized crystals to the X-ray beam intersection. This paper presents an improved design of an all-polymer microfluidic `chip' for room-temperature fixed-target serial crystallography that can be tailored to broadly meet the needs of users at either synchrotron or XFEL light sources. The chips are designed to be customized around different types of crystals and offer users a friendly, quick, convenient, ultra-low-cost and robust sample-delivery platform. Compared with the previous iteration of the chip [Gilbile et al. (2021), Lab Chip, 21, 4831-4845], the new design eliminates cleanroom fabrication. It has a larger imaging area to volume, while maintaining crystal hydration stability for both in situ crystallization or direct crystal slurry loading. Crystals of two model proteins, lysozyme and thaumatin, were used to validate the effectiveness of the design at both synchrotron (lysozyme and thaumatin) and XFEL (lysozyme only) facilities, yielding complete data sets with resolutions of 1.42, 1.48 and 1.70 Å, respectively. Overall, the improved chip design, ease of fabrication and high modifiability create a powerful, all-around sample-delivery tool that structural biologists can quickly adopt, especially in cases of limited sample volume and small, fragile crystals.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"944-952"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10565732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crystal structures of human and mouse ketohexokinase provide a structural basis for species- and isoform-selective inhibitor design. 人和小鼠酮己糖激酶的晶体结构为物种和异构体选择性抑制剂的设计提供了结构基础。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-10-01 Epub Date: 2023-09-15 DOI: 10.1107/S2059798323006137

Rebecca Ebenhoch, Margit Bauer, Helmut Romig, Dirk Gottschling, Jörg Thomas Kley, Niklas Heine, Alexander Weber, Ingo Uphues, Herbert Nar, Alexander Pautsch

引用次数: 0

Michael James (1940-2023). 迈克尔·詹姆斯（1940-2023）。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-10-01 Epub Date: 2023-09-15 DOI: 10.1107/S2059798323006976

J N Mark Glover, Cyril M Kay, Joanne Lemieux, Randy J Read

引用次数: 0

X-ray structure of the metastable SEPT14-SEPT7 coiled coil reveals a hendecad region crucial for heterodimerization. 亚稳SEPT14-SEPT7线圈的X射线结构揭示了一个对异二聚至关重要的hendeca区域。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-10-01 Epub Date: 2023-09-15 DOI: 10.1107/S2059798323006514

Italo A Cavini, Ashley J Winter, Humberto D'Muniz Pereira, Derek N Woolfson, Matthew P Crump, Richard C Garratt

{"title":"X-ray structure of the metastable SEPT14-SEPT7 coiled coil reveals a hendecad region crucial for heterodimerization.","authors":"Italo A Cavini, Ashley J Winter, Humberto D'Muniz Pereira, Derek N Woolfson, Matthew P Crump, Richard C Garratt","doi":"10.1107/S2059798323006514","DOIUrl":"10.1107/S2059798323006514","url":null,"abstract":"Septins are membrane-associated, GTP-binding proteins that are present in most eukaryotes. They polymerize to play important roles as scaffolds and/or diffusion barriers as part of the cytoskeleton. α-Helical coiled-coil domains are believed to contribute to septin assembly, and those observed in both human SEPT6 and SEPT8 form antiparallel homodimers. These are not compatible with their parallel heterodimeric organization expected from the current model for protofilament assembly, but they could explain the interfilament cross-bridges observed by microscopy. Here, the first structure of a heterodimeric septin coiled coil is presented, that between SEPT14 and SEPT7; the former is a SEPT6/SEPT8 homolog. This new structure is parallel, with two long helices that are axially shifted by a full helical turn with reference to their sequence alignment. The structure also has unusual knobs-into-holes packing of side chains. Both standard seven-residue (heptad) and the less common 11-residue (hendecad) repeats are present, creating two distinct regions with opposite supercoiling, which gives rise to an overall straight coiled coil. Part of the hendecad region is required for heterodimerization and therefore may be crucial for selective septin recognition. These unconventional sequences and structural features produce a metastable heterocomplex that nonetheless has enough specificity to promote correct protofilament assembly. For instance, the lack of supercoiling may facilitate unzipping and transitioning to the antiparallel homodimeric state.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"881-894"},"PeriodicalIF":2.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10565730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Raimond B. G. Ravelli (25 March 1968-30 June 2023). raymond B. G. Ravelli(1968年3月25日- 2023年6月30日)。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-09-01 DOI: 10.1107/S2059798323006897

Elspeth F Garman

引用次数: 0

A Python package based on robust statistical analysis for serial crystallography data processing. 基于稳健统计分析的 Python 软件包，用于序列晶体学数据处理。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-09-01 Epub Date: 2023-08-16 DOI: 10.1107/S2059798323005855

Marjan Hadian-Jazi, Alireza Sadri

{"title":"A Python package based on robust statistical analysis for serial crystallography data processing.","authors":"Marjan Hadian-Jazi, Alireza Sadri","doi":"10.1107/S2059798323005855","DOIUrl":"10.1107/S2059798323005855","url":null,"abstract":"The term robustness in statistics refers to methods that are generally insensitive to deviations from model assumptions. In other words, robust methods are able to preserve their accuracy even when the data do not perfectly fit the statistical models. Robust statistical analyses are particularly effective when analysing mixtures of probability distributions. Therefore, these methods enable the discretization of X-ray serial crystallography data into two probability distributions: a group comprising true data points (for example the background intensities) and another group comprising outliers (for example Bragg peaks or bad pixels on an X-ray detector). These characteristics of robust statistical analysis are beneficial for the ever-increasing volume of serial crystallography (SX) data sets produced at synchrotron and X-ray free-electron laser (XFEL) sources. The key advantage of the use of robust statistics for some applications in SX data analysis is that it requires minimal parameter tuning because of its insensitivity to the input parameters. In this paper, a software package called Robust Gaussian Fitting library (RGFlib) is introduced that is based on the concept of robust statistics. Two methods are presented based on the concept of robust statistics and RGFlib for two SX data-analysis tasks: (i) a robust peak-finding algorithm and (ii) an automated robust method to detect bad pixels on X-ray pixel detectors.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":"79 Pt 9","pages":"820-829"},"PeriodicalIF":2.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10521367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis of the amidase ClbL central to the biosynthesis of the genotoxin colibactin. 基因毒素可乐菌素生物合成的核心氨酶 ClbL 的结构基础。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-09-01 Epub Date: 2023-08-10 DOI: 10.1107/S2059798323005703

Prabhanshu Tripathi, Jarrod J Mousa, Naga Sandhya Guntaka, Steven D Bruner

{"title":"Structural basis of the amidase ClbL central to the biosynthesis of the genotoxin colibactin.","authors":"Prabhanshu Tripathi, Jarrod J Mousa, Naga Sandhya Guntaka, Steven D Bruner","doi":"10.1107/S2059798323005703","DOIUrl":"10.1107/S2059798323005703","url":null,"abstract":"Colibactin is a genotoxic natural product produced by select commensal bacteria in the human gut microbiota. The compound is a bis-electrophile that is predicted to form interstrand DNA cross-links in target cells, leading to double-strand DNA breaks. The biosynthesis of colibactin is carried out by a mixed NRPS-PKS assembly line with several noncanonical features. An amidase, ClbL, plays a key role in the pathway, catalyzing the final step in the formation of the pseudodimeric scaffold. ClbL couples α-aminoketone and β-ketothioester intermediates attached to separate carrier domains on the NRPS-PKS assembly. Here, the 1.9 Å resolution structure of ClbL is reported, providing a structural basis for this key step in the colibactin biosynthetic pathway. The structure reveals an open hydrophobic active site surrounded by flexible loops, and comparison with homologous amidases supports its unusual function and predicts macromolecular interactions with pathway carrier-protein substrates. Modeling protein-protein interactions supports a predicted molecular basis for enzyme-carrier domain interactions. Overall, the work provides structural insight into this unique enzyme that is central to the biosynthesis of colibactin.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":"79 Pt 9","pages":"830-836"},"PeriodicalIF":2.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10539163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LifeSoaks: a tool for analyzing solvent channels in protein crystals and obstacles for soaking experiments. lifeesoaks:一种分析蛋白质晶体中溶剂通道和浸泡实验障碍的工具。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-09-01 DOI: 10.1107/S205979832300582X

Jonathan Pletzer-Zelgert, Christiane Ehrt, Inken Fender, Axel Griewel, Florian Flachsenberg, Gerhard Klebe, Matthias Rarey

{"title":"LifeSoaks: a tool for analyzing solvent channels in protein crystals and obstacles for soaking experiments.","authors":"Jonathan Pletzer-Zelgert, Christiane Ehrt, Inken Fender, Axel Griewel, Florian Flachsenberg, Gerhard Klebe, Matthias Rarey","doi":"10.1107/S205979832300582X","DOIUrl":"https://doi.org/10.1107/S205979832300582X","url":null,"abstract":"Due to the structural complexity of proteins, their corresponding crystal arrangements generally contain a significant amount of solvent-occupied space. These areas allow a certain degree of intracrystalline protein flexibility and mobility of solutes. Therefore, knowledge of the geometry of solvent-filled channels and cavities is essential whenever the dynamics inside a crystal are of interest. Especially in soaking experiments for structure-based drug design, ligands must be able to traverse the crystal solvent channels and reach the corresponding binding pockets. Unsuccessful screenings are sometimes attributed to the geometry of the crystal packing, but the underlying causes are often difficult to understand. This work presents LifeSoaks, a novel tool for analyzing and visualizing solvent channels in protein crystals. LifeSoaks uses a Voronoi diagram-based periodic channel representation which can be efficiently computed. The size and location of channel bottlenecks, which might hinder molecular diffusion, can be directly derived from this representation. This work presents the calculated bottleneck radii for all crystal structures in the PDB and the analysis of a new, hand-curated data set of structures obtained by soaking experiments. The results indicate that the consideration of bottleneck radii and the visual inspection of channels are beneficial for planning soaking experiments.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":"79 Pt 9","pages":"837-856"},"PeriodicalIF":2.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10539167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel starting points for fragment-based drug design against mycobacterial thioredoxin reductase identified using crystallographic fragment screening. 利用结晶学片段筛选确定的针对分枝杆菌硫氧还蛋白还原酶的基于片段的药物设计的新起点。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-09-01 DOI: 10.1107/S2059798323005223

Friederike T Füsser, Jan Wollenhaupt, Manfred S Weiss, Daniel Kümmel, Oliver Koch

{"title":"Novel starting points for fragment-based drug design against mycobacterial thioredoxin reductase identified using crystallographic fragment screening.","authors":"Friederike T Füsser, Jan Wollenhaupt, Manfred S Weiss, Daniel Kümmel, Oliver Koch","doi":"10.1107/S2059798323005223","DOIUrl":"https://doi.org/10.1107/S2059798323005223","url":null,"abstract":"The increasing number of people dying from tuberculosis and the existence of extensively drug-resistant strains has led to an urgent need for new antituberculotic drugs with alternative modes of action. As part of the thioredoxin system, thioredoxin reductase (TrxR) is essential for the survival of Mycobacterium tuberculosis (Mtb) and shows substantial differences from human TrxR, making it a promising and most likely selective target. As a model organism for Mtb, crystals of Mycobacterium smegmatis TrxR that diffracted to high resolution were used in crystallographic fragment screening to discover binding fragments and new binding sites. The application of the 96 structurally diverse fragments from the F2X-Entry Screen revealed 56 new starting points for fragment-based drug design of new TrxR inhibitors. Over 200 crystal structures were analyzed using FragMAXapp, which includes processing and refinement by largely automated software pipelines and hit identification via the multi-data-set analysis approach PanDDA. The fragments are bound to 11 binding sites, of which four are positioned at binding pockets or important interaction sites and therefore show high potential for possible inhibition of TrxR.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":"79 Pt 9","pages":"857-865"},"PeriodicalIF":2.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0