Acta Crystallographica. Section D, Structural Biology最新文献_第8页

The crystal structure of mycothiol disulfide reductase (Mtr) provides mechanistic insight into the specific low-molecular-weight thiol reductase activity of Actinobacteria. 霉菌硫醇二硫还原酶（Mtr）的晶体结构从机理上揭示了放线菌特异的低分子量硫醇还原酶活性。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-03-01 Epub Date: 2024-02-19 DOI: 10.1107/S205979832400113X

Javier Gutiérrez-Fernández, Hans Petter Hersleth, Marta Hammerstad

{"title":"The crystal structure of mycothiol disulfide reductase (Mtr) provides mechanistic insight into the specific low-molecular-weight thiol reductase activity of Actinobacteria.","authors":"Javier Gutiérrez-Fernández, Hans Petter Hersleth, Marta Hammerstad","doi":"10.1107/S205979832400113X","DOIUrl":"10.1107/S205979832400113X","url":null,"abstract":"Low-molecular-weight (LMW) thiols are involved in many processes in all organisms, playing a protective role against reactive species, heavy metals, toxins and antibiotics. Actinobacteria, such as Mycobacterium tuberculosis, use the LMW thiol mycothiol (MSH) to buffer the intracellular redox environment. The NADPH-dependent FAD-containing oxidoreductase mycothiol disulfide reductase (Mtr) is known to reduce oxidized mycothiol disulfide (MSSM) to MSH, which is crucial to maintain the cellular redox balance. In this work, the first crystal structures of Mtr are presented, expanding the structural knowledge and understanding of LMW thiol reductases. The structural analyses and docking calculations provide insight into the nature of Mtrs, with regard to the binding and reduction of the MSSM substrate, in the context of related oxidoreductases. The putative binding site for MSSM suggests a similar binding to that described for the homologous glutathione reductase and its respective substrate glutathione disulfide, but with distinct structural differences shaped to fit the bulkier MSSM substrate, assigning Mtrs as uniquely functioning reductases. As MSH has been acknowledged as an attractive antitubercular target, the structural findings presented in this work may contribute towards future antituberculosis drug development.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"181-193"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10910545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899183","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

Welcoming five new Co-editors. 欢迎五位新任联合编辑。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-03-01 Epub Date: 2024-02-29 DOI: 10.1107/S2059798324002006

Charles S Bond, Elspeth F Garman, Randy J Read

引用次数: 0

Advanced exploitation of unmerged reflection data during processing and refinement with autoPROC and BUSTER. 利用 autoPROC 和 BUSTER，在处理和细化过程中对未合并的反射数据进行高级开发。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-03-01 Epub Date: 2024-02-27 DOI: 10.1107/S2059798324001487

Clemens Vonrhein, Claus Flensburg, Peter Keller, Rasmus Fogh, Andrew Sharff, Ian J Tickle, Gérard Bricogne

{"title":"Advanced exploitation of unmerged reflection data during processing and refinement with autoPROC and BUSTER.","authors":"Clemens Vonrhein, Claus Flensburg, Peter Keller, Rasmus Fogh, Andrew Sharff, Ian J Tickle, Gérard Bricogne","doi":"10.1107/S2059798324001487","DOIUrl":"10.1107/S2059798324001487","url":null,"abstract":"The validation of structural models obtained by macromolecular X-ray crystallography against experimental diffraction data, whether before deposition into the PDB or after, is typically carried out exclusively against the merged data that are eventually archived along with the atomic coordinates. It is shown here that the availability of unmerged reflection data enables valuable additional analyses to be performed that yield improvements in the final models, and tools are presented to implement them, together with examples of the results to which they give access. The first example is the automatic identification and removal of image ranges affected by loss of crystal centering or by excessive decay of the diffraction pattern as a result of radiation damage. The second example is the `reflection-auditing' process, whereby individual merged data items showing especially poor agreement with model predictions during refinement are investigated thanks to the specific metadata (such as image number and detector position) that are available for the corresponding unmerged data, potentially revealing previously undiagnosed instrumental, experimental or processing problems. The third example is the calculation of so-called F(early) - F(late) maps from carefully selected subsets of unmerged amplitude data, which can not only highlight the location and extent of radiation damage but can also provide guidance towards suitable fine-grained parametrizations to model the localized effects of such damage.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"148-158"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10910543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970604","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

Using cryo-EM to understand the assembly pathway of respiratory complex I. 利用低温电子显微镜了解呼吸复合体 I 的组装途径。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-03-01 Epub Date: 2024-02-19 DOI: 10.1107/S205979832400086X

Eike Laube, Jonathan Schiller, Volker Zickermann, Janet Vonck

引用次数: 0

Investigation of how gate residues in the main channel affect the catalytic activity of Scytalidium thermophilum catalase. 研究主通道中的门残基如何影响嗜热菌过氧化氢酶的催化活性。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-02-01 Epub Date: 2024-01-24 DOI: 10.1107/S2059798323011063

Yonca Yuzugullu Karakus, Gunce Goc, Melis Zengin Karatas, Sinem Balci Unver, Briony A Yorke, Arwen R Pearson

{"title":"Investigation of how gate residues in the main channel affect the catalytic activity of Scytalidium thermophilum catalase.","authors":"Yonca Yuzugullu Karakus, Gunce Goc, Melis Zengin Karatas, Sinem Balci Unver, Briony A Yorke, Arwen R Pearson","doi":"10.1107/S2059798323011063","DOIUrl":"10.1107/S2059798323011063","url":null,"abstract":"Catalase is an antioxidant enzyme that breaks down hydrogen peroxide (H2O2) into molecular oxygen and water. In all monofunctional catalases the pathway that H2O2 takes to the catalytic centre is via the `main channel'. However, the structure of this channel differs in large-subunit and small-subunit catalases. In large-subunit catalases the channel is 15 Å longer and consists of two distinct parts, including a hydrophobic lower region near the heme and a hydrophilic upper region where multiple H2O2 routes are possible. Conserved glutamic acid and threonine residues are located near the intersection of these two regions. Mutations of these two residues in the Scytalidium thermophilum catalase had no significant effect on catalase activity. However, the secondary phenol oxidase activity was markedly altered, with kcat and kcat/Km values that were significantly increased in the five variants E484A, E484I, T188D, T188I and T188F. These variants also showed a lower affinity for inhibitors of oxidase activity than the wild-type enzyme and a higher affinity for phenolic substrates. Oxidation of heme b to heme d did not occur in most of the studied variants. Structural changes in solvent-chain integrity and channel architecture were also observed. In summary, modification of the main-channel gate glutamic acid and threonine residues has a greater influence on the secondary activity of the catalase enzyme, and the oxidation of heme b to heme d is predominantly inhibited by their conversion to aliphatic and aromatic residues.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"101-112"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545257","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

Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket. 以 SARS-CoV-2 主要蛋白酶结合口袋的开放形式为目标的片段筛选。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI: 10.1107/S2059798324000329

Chia Ying Huang, Alexander Metz, Roland Lange, Nadia Artico, Céline Potot, Julien Hazemann, Manon Müller, Marina Dos Santos, Alain Chambovey, Daniel Ritz, Deniz Eris, Solange Meyer, Geoffroy Bourquin, May Sharpe, Aengus Mac Sweeney

{"title":"Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket.","authors":"Chia Ying Huang, Alexander Metz, Roland Lange, Nadia Artico, Céline Potot, Julien Hazemann, Manon Müller, Marina Dos Santos, Alain Chambovey, Daniel Ritz, Deniz Eris, Solange Meyer, Geoffroy Bourquin, May Sharpe, Aengus Mac Sweeney","doi":"10.1107/S2059798324000329","DOIUrl":"10.1107/S2059798324000329","url":null,"abstract":"To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"123-136"},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641430","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

Deciphering the crystal structure of a novel nanobody against the NEIL1 DNA glycosylase. 解密针对 NEIL1 DNA 糖基化酶的新型纳米抗体的晶体结构。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI: 10.1107/S205979832400038X

Marlo K Thompson, Nidhi Sharma, Andrea Thorn, Aishwarya Prakash

引用次数: 0

Current trends in macromolecular model refinement and validation. 大分子模型完善和验证的当前趋势。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-01-01 DOI: 10.1107/S2059798323010823

Melanie Vollmar, Robert Nicholls, Svetlana Antonyuk

引用次数: 0

Preparation and characterization of inactivated tick-borne encephalitis virus samples for single-particle imaging at the European XFEL. 用于欧洲 XFEL 单粒子成像的灭活蜱传脑炎病毒样本的制备和特征描述。

IF 2.2 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-01-01 DOI: 10.1107/S2059798323010562

Mikhail F Vorovitch, Valeriya R Samygina, Evgeny Pichkur, Peter V Konarev, Georgy Peters, Evgeny V Khvatov, Alla L Ivanova, Ksenia K Tuchynskaya, Olga I Konyushko, Anton Y Fedotov, Grigory Armeev, Konstantin V Shaytan, Mikhail V Kovalchuk, Dmitry I Osolodkin, Alexey M Egorov, Aydar A Ishmukhametov

{"title":"Preparation and characterization of inactivated tick-borne encephalitis virus samples for single-particle imaging at the European XFEL.","authors":"Mikhail F Vorovitch, Valeriya R Samygina, Evgeny Pichkur, Peter V Konarev, Georgy Peters, Evgeny V Khvatov, Alla L Ivanova, Ksenia K Tuchynskaya, Olga I Konyushko, Anton Y Fedotov, Grigory Armeev, Konstantin V Shaytan, Mikhail V Kovalchuk, Dmitry I Osolodkin, Alexey M Egorov, Aydar A Ishmukhametov","doi":"10.1107/S2059798323010562","DOIUrl":"10.1107/S2059798323010562","url":null,"abstract":"X-ray imaging of virus particles at the European XFEL could eventually allow their complete structures to be solved, potentially approaching the resolution of other structural virology methods. To achieve this ambitious goal with today's technologies, about 1 ml of purified virus suspension containing at least 1012 particles per millilitre is required. Such large amounts of concentrated suspension have never before been obtained for enveloped viruses. Tick-borne encephalitis virus (TBEV) represents an attractive model system for the development of enveloped virus purification and concentration protocols, given the availability of large amounts of inactivated virus material provided by vaccine-manufacturing facilities. Here, the development of a TBEV vaccine purification and concentration scheme is presented combined with a quality-control protocol that allows substantial amounts of highly concentrated non-aggregated suspension to be obtained. Preliminary single-particle imaging experiments were performed for this sample at the European XFEL, showing distinct diffraction patterns.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"44-59"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139072972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep residual networks for crystallography trained on synthetic data. 基于合成数据训练的晶体学深度残差网络。

IF 2.6 4区生物学

Acta Crystallographica. Section D, Structural Biology Pub Date : 2024-01-01 DOI: 10.1107/S2059798323010586

Derek Mendez, James M Holton, Artem Y Lyubimov, Sabine Hollatz, Irimpan I Mathews, Aleksander Cichosz, Vardan Martirosyan, Teo Zeng, Ryan Stofer, Ruobin Liu, Jinhu Song, Scott McPhillips, Mike Soltis, Aina E Cohen

{"title":"Deep residual networks for crystallography trained on synthetic data.","authors":"Derek Mendez, James M Holton, Artem Y Lyubimov, Sabine Hollatz, Irimpan I Mathews, Aleksander Cichosz, Vardan Martirosyan, Teo Zeng, Ryan Stofer, Ruobin Liu, Jinhu Song, Scott McPhillips, Mike Soltis, Aina E Cohen","doi":"10.1107/S2059798323010586","DOIUrl":"10.1107/S2059798323010586","url":null,"abstract":"The use of artificial intelligence to process diffraction images is challenged by the need to assemble large and precisely designed training data sets. To address this, a codebase called Resonet was developed for synthesizing diffraction data and training residual neural networks on these data. Here, two per-pattern capabilities of Resonet are demonstrated: (i) interpretation of crystal resolution and (ii) identification of overlapping lattices. Resonet was tested across a compilation of diffraction images from synchrotron experiments and X-ray free-electron laser experiments. Crucially, these models readily execute on graphics processing units and can thus significantly outperform conventional algorithms. While Resonet is currently utilized to provide real-time feedback for macromolecular crystallography users at the Stanford Synchrotron Radiation Lightsource, its simple Python-based interface makes it easy to embed in other processing frameworks. This work highlights the utility of physics-based simulation for training deep neural networks and lays the groundwork for the development of additional models to enhance diffraction collection and analysis.","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":" ","pages":"26-43"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10833344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139072971","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