Acta Crystallographica Section D最新文献

Crystallographic fragment screening against SARS-CoV-2 nonstructural protein 1 using the F2X-Entry Screen and a newly developed fragment library. 利用F2X-Entry Screen和新开发的片段库对SARS-CoV-2非结构蛋白1进行晶体学片段筛选。

Acta Crystallographica Section D Pub Date : 2025-11-01 DOI: 10.1107/s2059798325008563

Frank Lennartz,Jan Wollenhaupt,Melanie Oelker,Paula Fröling,Uwe Mueller,Anke Deckers,Christoph Grathwol,Stefan Bräse,Nicole Jung,Manfred S Weiss

{"title":"Crystallographic fragment screening against SARS-CoV-2 nonstructural protein 1 using the F2X-Entry Screen and a newly developed fragment library.","authors":"Frank Lennartz,Jan Wollenhaupt,Melanie Oelker,Paula Fröling,Uwe Mueller,Anke Deckers,Christoph Grathwol,Stefan Bräse,Nicole Jung,Manfred S Weiss","doi":"10.1107/s2059798325008563","DOIUrl":"https://doi.org/10.1107/s2059798325008563","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten global health. This underpins the need for novel therapeutics against this virus. Nonstructural protein 1 (Nsp1) of SARS-CoV-2 is a multifunctional protein with an essential role in viral replication. As such, it presents itself as an attractive target for drug discovery. Here, we describe two crystallographic fragment-screening campaigns against Nsp1, one using the established F2X-Entry Screen and one using a new, chemically and structurally diverse fragment library, which we call the KIT library. Together, 21 hits could be identified from 192 screened fragments, which constitutes the highest hit rate reported for Nsp1 to date. Many hits bind to a key functional region and interact with residues involved in cellular mRNA cleavage, ribosome binding and viral RNA recognition. Furthermore, most of the identified fragments share a common binding mode, providing promising starting points for further optimization into drug-like compounds that can disrupt the role of Nsp1 in viral replication.","PeriodicalId":501686,"journal":{"name":"Acta Crystallographica Section D","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Critical evaluation of three cryo-EM structures of particulate methane monooxygenase by quantum refinement. 用量子精细化对颗粒甲烷单加氧酶的三种低温电镜结构进行了关键性评价。

Acta Crystallographica Section D Pub Date : 2025-11-01 DOI: 10.1107/s2059798325008356

Gayathri Yuvaraj,Kristoffer J M Lundgren,Elija Veenman,Esko Oksanen,Ulf Ryde

{"title":"Critical evaluation of three cryo-EM structures of particulate methane monooxygenase by quantum refinement.","authors":"Gayathri Yuvaraj,Kristoffer J M Lundgren,Elija Veenman,Esko Oksanen,Ulf Ryde","doi":"10.1107/s2059798325008356","DOIUrl":"https://doi.org/10.1107/s2059798325008356","url":null,"abstract":"Particulate methane monooxygenase (pMMO) is an enzyme that converts methane into methanol at ambient temperature and pressure. Over the past three decades, the metal content and location of the active site have been highly controversial. Recent single-particle cryogenic electron-microscopy (cryo-EM) structures have furthered this debate. In this study, three cryo-EM structures (PDB entries 7s4h, 7s4j and 7ev9) are analysed by quantum refinement (QR). This approach augments traditional structural refinement with quantum-mechanical (QM) calculations for a small but interesting part of the protein (in this case, the copper sites). Our results indicate that the bis-His (CuA) site is correctly modelled as a mononuclear copper site in all three structures. The His-brace (CuB) site is also best modelled as mononuclear in all structures, although it was suggested to be a binuclear site in PDB entry 7ev9. The CuC site, which is observed only in PDB entry 7s4j, is correctly modelled and is probably reduced in the structure. The CuD putative active site, observed only in PDB entry 7s4h, is also mononuclear, but a water molecule might at least intermittently coordinate to the copper ion. On the other hand, our study does not find any support for the five additional copper ions suggested to be present in PDB entry 7ev9, including the suggested trinuclear active site and two sites in the so-called copper sponge. Instead, more chemically reasonable structures and better fit to both the cryo-EM and QM data are obtained if these copper ions are replaced with water molecules. This study illustrates the potential of QR as a standard component of cryo-EM studies for metal sites, for which reliable empirical restraints are missing.","PeriodicalId":501686,"journal":{"name":"Acta Crystallographica Section D","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How many (distinguishable) classes can we identify in single-particle analysis? 在单粒子分析中，我们可以识别出多少（可区分的）类别？

Acta Crystallographica Section D Pub Date : 2025-10-01 DOI: 10.1107/s2059798325007831

O Lauzirika,M Pernica,D Herreros,E Ramírez-Aportela,J Krieger,M Gragera,M Iceta,P Conesa,Y Fonseca,J Jiménez,J Filipovic,J M Carazo,C O S Sorzano

引用次数: 0

Categorizing prediction modes within low-pLDDT regions of AlphaFold2 structures: near-predictive, pseudostructure and barbed wire. AlphaFold2结构低plddt区域的分类预测模式：近预测、伪结构和铁丝网。

Acta Crystallographica Section D Pub Date : 2025-10-01 DOI: 10.1107/s2059798325007843

Christopher J Williams,Vincent B Chen,David C Richardson,Jane S Richardson

{"title":"Categorizing prediction modes within low-pLDDT regions of AlphaFold2 structures: near-predictive, pseudostructure and barbed wire.","authors":"Christopher J Williams,Vincent B Chen,David C Richardson,Jane S Richardson","doi":"10.1107/s2059798325007843","DOIUrl":"https://doi.org/10.1107/s2059798325007843","url":null,"abstract":"AlphaFold2 protein structure predictions are widely available for structural biology uses. These predictions, especially for eukaryotic proteins, frequently contain extensive regions predicted below the pLDDT = 70 level, the rule-of-thumb cutoff for high confidence. This work identifies major modes of behavior within low-pLDDT regions through a survey of human proteome predictions provided by the AlphaFold Protein Structure Database. The near-predictive mode resembles folded protein and can be a nearly accurate prediction. Barbed wire is extremely unprotein-like, being recognized by wide looping coils, an absence of packing contacts and numerous signature validation outliers, and it represents a region where the conformation has no predictive value. Pseudostructure presents an intermediate behavior with a misleading appearance of isolated and badly formed secondary-structure-like elements. These prediction modes are compared with annotations of disorder from MobiDB, showing general correlation between barbed wire/pseudostructure and many measures of disorder, an association between pseudostructure and signal peptides, and an association between near-predictive and regions of conditional folding. To enable users to identify these regions within a prediction, a new Phenix tool is developed encompassing the results of this work, including prediction annotation, visual markup and residue selection based on these prediction modes. This tool will help users develop expertise in interpreting difficult AlphaFold predictions and identify the near-predictive regions that can aid in molecular replacement when a prediction does not contain enough high-pLDDT regions.","PeriodicalId":501686,"journal":{"name":"Acta Crystallographica Section D","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Room-temperature X-ray data collection enabled the structural determination of statin-bound CYP105A1. 室温x射线数据收集能够确定他汀结合CYP105A1的结构。

Acta Crystallographica Section D Pub Date : 2025-10-01 DOI: 10.1107/s2059798325007673

Teisuke Takita,Sachiyo Yoneda,Kaori Yasuda,Kimihiko Mizutani,Kiyoshi Yasukawa,Toshiyuki Sakaki,Bunzo Mikami

{"title":"Room-temperature X-ray data collection enabled the structural determination of statin-bound CYP105A1.","authors":"Teisuke Takita,Sachiyo Yoneda,Kaori Yasuda,Kimihiko Mizutani,Kiyoshi Yasukawa,Toshiyuki Sakaki,Bunzo Mikami","doi":"10.1107/s2059798325007673","DOIUrl":"https://doi.org/10.1107/s2059798325007673","url":null,"abstract":"Streptomyces griseolus CYP105A1 exhibits monooxygenase activity towards a wide variety of structurally diverse substrates with regiospecificity and stereospecificity, making it suitable for broad applications. Our previous studies have demonstrated that both wild-type CYP105A1 and its mutants metabolize vitamin D3 and its derivatives, as well as 12 types of nonsteroidal anti-inflammatory drugs (NSAIDs) and statins. Notably, the R84A mutant displayed high activity against vitamin D3, numerous NSAIDs and statins. Although we were unable to obtain CYP105A1-statin complex structures through co-crystallization and standard cryo data collection, we successfully acquired complex structures with mevastatin and simvastatin using room-temperature data collection with a conventional capillary method. We observed that the reduced unit-cell dimensions of the cryo crystals resulted in increased symmetry interactions, which induced cis-trans conversion of the peptide bond between Pro142 and Thr143 and conformational changes in the residues critical for statin binding. It is suggested that these increased symmetry interactions in the cryo crystals lead to dissociation of the statins from the active site of the enzyme.","PeriodicalId":501686,"journal":{"name":"Acta Crystallographica Section D","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biophysical Chemistry, Second Edition. By Dagmar Klostermeier and Markus G. Rudolph. CRC Press, Boca Raton, 2025, pp. 944. ISBN 9781032060835. Price GBP 57.39 (hardback). 生物物理化学，第二版。达格玛·克劳斯特迈尔和马库斯·g·鲁道夫著。CRC出版社，博卡拉顿，2025年，第944页。ISBN 9781032060835。价格57.39英镑（精装本）。

Acta Crystallographica Section D Pub Date : 2025-10-01 DOI: 10.1107/s2059798325007764

Marc Hebrant

引用次数: 0

Perspective on structure predictions of disorder. 对无序结构预测的展望。

Acta Crystallographica Section D Pub Date : 2025-09-30 DOI: 10.1107/s2059798325008599

Charles S Bond

引用次数: 0

Rengachary Parthasarathy (1939-2025): a life journey from Nagari to San Jose. Rengachary Parthasarathy(1939-2025)：从纳加里到圣何塞的人生旅程。

Acta Crystallographica Section D Pub Date : 2025-09-01 DOI: 10.1107/s205979832500628x

S Narasinga Rao,Manuel Soriano Garcia

引用次数: 0

Crystal structure of the β2-microglobulin-BBM.1 antibody complex reveals the molecular basis of antigen recognition. β2-微球蛋白- bbm的晶体结构。1抗体复合物揭示抗原识别的分子基础。

Acta Crystallographica Section D Pub Date : 2025-09-01 DOI: 10.1107/s2059798325006370

Jiajia Wu,Fuming Zeng,Xiaorong Wang,Pengcheng Wei

{"title":"Crystal structure of the β2-microglobulin-BBM.1 antibody complex reveals the molecular basis of antigen recognition.","authors":"Jiajia Wu,Fuming Zeng,Xiaorong Wang,Pengcheng Wei","doi":"10.1107/s2059798325006370","DOIUrl":"https://doi.org/10.1107/s2059798325006370","url":null,"abstract":"β2-Microglobulin (β2M) is an essential component of major histocompatibility complex class I (MHC-I) molecules, with a well established canonical role in immune surveillance. Beyond its classical functions, accumulating evidence has highlighted β2M as a multifaceted biomarker, with elevated serum levels closely associated with disease burden and prognosis in metabolic disorders, malignancies, autoimmune diseases and central nervous system conditions. In this study, we resolved the crystal structure of human β2M in complex with the mouse monoclonal antibody BBM.1 at 2.50 Å resolution using X-ray crystallography. Structural analysis revealed that BBM.1 binds β2M through multiple CDRs, recognizing key surface residues including Glu36, Asp38, Lys41, Asn42, Glu44, Arg45, Glu47 and Arg81. The interaction is anchored by a central hydrophobic core formed by Trp32 (light chain), Trp99 (heavy chain) and Ile92 (β2M), which is deeply buried in the interface. Surrounding this core is a well organized polar interaction network composed of hydrogen bonds and salt bridges, primarily involving β2M residues Lys41, Glu44, Arg45 and Glu47. Notably, the Arg45 residue deeply embeds into the antibody-binding pocket, forming several crucial interactions. These findings not only validate previous biochemical and mutational data but also identify new epitope residues, providing a structural foundation for the development and optimization of precision therapeutic strategies targeting β2M.","PeriodicalId":501686,"journal":{"name":"Acta Crystallographica Section D","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

XFBLD-Platform: a crystallographic fragment-screening platform at Shanghai Synchrotron Radiation Facility. xfbld平台：上海同步辐射设施的晶体碎片筛选平台。

Acta Crystallographica Section D Pub Date : 2025-09-01 DOI: 10.1107/s2059798325006801

Liqing Huang,Weiwei Wang,Zhimin Zhu,Qianhui Li,Minjun Li,Huan Zhou,Qin Xu,Qisheng Wang,Feng Yu

引用次数: 0