Current Research in Structural Biology最新文献_第4页

Assessment of Kaistella jeonii esterase conformational dynamics in response to poly(ethylene terephthalate) binding 评估Kaistella jeonii酯酶与聚对苯二甲酸乙二醇酯结合时的构象动态

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100130

Ederson Sales Moreira Pinto , Arthur Tonietto Mangini , Lorenzo Chaves Costa Novo , Fernando Guimaraes Cavatao , Mathias J. Krause , Marcio Dorn

{"title":"Assessment of Kaistella jeonii esterase conformational dynamics in response to poly(ethylene terephthalate) binding","authors":"Ederson Sales Moreira Pinto , Arthur Tonietto Mangini , Lorenzo Chaves Costa Novo , Fernando Guimaraes Cavatao , Mathias J. Krause , Marcio Dorn","doi":"10.1016/j.crstbi.2024.100130","DOIUrl":"10.1016/j.crstbi.2024.100130","url":null,"abstract":"<div><p>The pervasive presence of plastic in the environment has reached a concerning scale, being identified in many ecosystems. Bioremediation is the cheapest and most eco-friendly alternative to remove this polymer from affected areas. Recent work described that a novel cold-active esterase enzyme extracted from the bacteria <em>Kaistella jeonii</em> could promiscuously degrade PET. Compared to the well-known PETase from <em>Ideonella sakaiensis</em>, this novel esterase presents a low sequence identity yet has a remarkably similar folding. However, enzymatic assays demonstrated a lower catalytic efficiency. In this work, we employed a strict computational approach to investigate the binding mechanism between the esterase and PET. Understanding the underlying mechanism of binding can shed light on the evolutive mechanism of how enzymes have been evolving to degrade these artificial molecules and help develop rational engineering approaches to improve PETase-like enzymes. Our results indicate that this esterase misses a disulfide bridge, keeping the catalytic residues closer and possibly influencing its catalytic efficiency. Moreover, we describe the structural response to the interaction between enzyme and PET, indicating local and global effects. Our results aid in deepening the knowledge behind the mechanism of biological catalysis of PET degradation and as a base for the engineering of novel PETases.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100130"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000072/pdfft?md5=33dd0e45dffd911f763970f961540bfb&pid=1-s2.0-S2665928X24000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139889948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SAGESDA: Multi-GraphSAGE networks for predicting SnoRNA-disease associations SAGESDA：预测 SnoRNA 与疾病关联的多图 SAGE 网络

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2023.100122

Biffon Manyura Momanyi , Yu-Wei Zhou , Bakanina Kissanga Grace-Mercure , Sebu Aboma Temesgen , Ahmad Basharat , Lin Ning , Lixia Tang , Hui Gao , Hao Lin , Hua Tang

{"title":"SAGESDA: Multi-GraphSAGE networks for predicting SnoRNA-disease associations","authors":"Biffon Manyura Momanyi , Yu-Wei Zhou , Bakanina Kissanga Grace-Mercure , Sebu Aboma Temesgen , Ahmad Basharat , Lin Ning , Lixia Tang , Hui Gao , Hao Lin , Hua Tang","doi":"10.1016/j.crstbi.2023.100122","DOIUrl":"https://doi.org/10.1016/j.crstbi.2023.100122","url":null,"abstract":"<div><p>Over the years, extensive research has highlighted the functional roles of small nucleolar RNAs in various biological processes associated with the development of complex human diseases. Therefore, understanding the existing relationships between different snoRNAs and diseases is crucial for advancing disease diagnosis and treatment. However, classical biological experiments for identifying snoRNA-disease associations are expensive and time-consuming. Therefore, there is an urgent need for cost-effective computational techniques that can enhance the efficiency and accuracy of prediction. While several computational models have already been proposed, many suffer from limitations and suboptimal performance. In this study, we introduced a novel Graph Neural Network-based (GNN) classification model, called SAGESDA, which is implemented through the GraphSAGE architecture with attention for the prediction of snoRNA-disease associations. The classifier leverages local neighbouring nodes in a heterogeneous network to generate new node embeddings through message passing. The mini-batch gradient descent technique was applied to divide the graph into smaller sub-graphs, which enhances the model's accuracy, speed and scalability. With these advancements, SAGESDA attained an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92 using the standard dot product classifier, surpassing previous related studies. This notable performance demonstrates that SAGESDA is a promising model for predicting unknown snoRNA-disease associations with high accuracy. The SAGESDA implementation details can be obtained from <span>https://github.com/momanyibiffon/SAGESDA.git</span><svg><path></path></svg>.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100122"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X23000284/pdfft?md5=53e908984f68e8f4f39afb0050a896ca&pid=1-s2.0-S2665928X23000284-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinformatic analysis of THAP9 transposase homolog: conserved regions, novel motifs THAP9 转座酶同源物的生物信息学分析：保守区域和新图案

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2023.100113

Richa Rashmi , Chandan Nandi , Sharmistha Majumdar

{"title":"Bioinformatic analysis of THAP9 transposase homolog: conserved regions, novel motifs","authors":"Richa Rashmi , Chandan Nandi , Sharmistha Majumdar","doi":"10.1016/j.crstbi.2023.100113","DOIUrl":"10.1016/j.crstbi.2023.100113","url":null,"abstract":"<div><p>THAP9 is a transposable element-derived gene that encodes the THAP9 protein, which is homologous to the <em>Drosophila</em> P-element transposase (DmTNP) and can cut and paste DNA. However, the exact functional role of THAP9 is unknown. Here, we perform structure prediction, evolutionary analysis and extensive <em>in silico</em> characterization of THAP9, including predicting domains and putative post-translational modification sites. Comparison of the AlphaFold-predicted structure of THAP9 with the DmTNP CryoEM structure, provided insights about the C2CH motif and other DNA binding residues, RNase H-like catalytic domain and insertion domain of the THAP9 protein. We also predicted previously unreported mammalian-specific post-translational modification sites that may play a role in the subcellular localization of THAP9. Furthermore, we observed that there are distinct organism class-specific conservation patterns of key functional residues in certain THAP9 domains.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100113"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X23000193/pdfft?md5=c3c5880ce6446e6690c6b1d1b686feff&pid=1-s2.0-S2665928X23000193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139293648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 and functional profile of phytases across the domains of life 各生命领域植酸酶的结构和功能概况

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100139

Benjamin M. Scott , Kevin Koh , Gregory D. Rix

引用次数: 0

Computational identification of candidate inhibitors for Dihydrofolate reductase in Acinetobacter baumannii 鲍曼不动杆菌二氢叶酸还原酶候选抑制剂的计算鉴定

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100127

Saurabh Kumar Bhati, Monika Jain, Jayaraman Muthukumaran, Amit Kumar Singh

{"title":"Computational identification of candidate inhibitors for Dihydrofolate reductase in Acinetobacter baumannii","authors":"Saurabh Kumar Bhati, Monika Jain, Jayaraman Muthukumaran, Amit Kumar Singh","doi":"10.1016/j.crstbi.2024.100127","DOIUrl":"10.1016/j.crstbi.2024.100127","url":null,"abstract":"<div><p><em>Acinetobacter baumannii</em> is one of the emerging causes of hospital acquired infections and this bacterium, due to multi-drug resistant and Extensive Drug resistant has been able to develop resistance against the antimicrobial agents that are being used to eliminate it. <em>A.baumannii</em> has been the cause of death in immune compromised patients in hospitals. Hence it is the urgent need of time to find potential inhibitors for this bacterium to cease its virulence and affect its survival inside host organisms. The Dihydrofolate reductase enzyme, which is an important biocatalyst in the conversion of Dihydrofolate to Tetrahydrofolate, is an important drug target protein. In the present study high throughput screening is used to identify the inhibitors of this enzyme. The prioritized ligand molecular candidates identified through virtual screening for the substrate binding site of the predicted model are Z1447621107, Z2604448220 and Z1830442365. The Molecular Dynamics Simulation study suggests that potential inhibitor of the Dihydrofolate reductase enzyme would prevent bacteria from completing its life cycle, affecting its survival. Finally the complexes were analysed for binding free energy of the Dihydrofolate reductase enzyme complexes with the ligands.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100127"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000047/pdfft?md5=f83d409176a71f1deed39eeb70ffa0bd&pid=1-s2.0-S2665928X24000047-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139635556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The active site of the SGNH hydrolase-like fold proteins: Nucleophile–oxyanion (Nuc-Oxy) and Acid–Base zones SGNH 水解酶样折叠蛋白的活性位点：亲核-亲氧（Nuc-Oxy）区和酸碱区

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2023.100123

Konstantin Denessiouk , Alexander I. Denesyuk , Sergei E. Permyakov , Eugene A. Permyakov , Mark S. Johnson , Vladimir N. Uversky

{"title":"The active site of the SGNH hydrolase-like fold proteins: Nucleophile–oxyanion (Nuc-Oxy) and Acid–Base zones","authors":"Konstantin Denessiouk , Alexander I. Denesyuk , Sergei E. Permyakov , Eugene A. Permyakov , Mark S. Johnson , Vladimir N. Uversky","doi":"10.1016/j.crstbi.2023.100123","DOIUrl":"https://doi.org/10.1016/j.crstbi.2023.100123","url":null,"abstract":"<div><p>SGNH hydrolase-like fold proteins are serine proteases with the default Asp-His-Ser catalytic triad. Here, we show that these proteins share two unique conserved structural organizations around the active site: (1) the Nuc-Oxy Zone around the catalytic nucleophile and the oxyanion hole, and (2) the Acid-Base Zone around the catalytic acid and base. The Nuc-Oxy Zone consists of 14 amino acids cross-linked with eight conserved intra- and inter-block hydrogen bonds. The Acid–Base Zone is constructed from a single fragment of the polypeptide chain, which incorporates both the catalytic acid and base, and whose N- and C-terminal residues are linked together by a conserved hydrogen bond. The Nuc-Oxy and Acid-Base Zones are connected by an SHLink, a two-bond conserved interaction from amino acids, adjacent to the catalytic nucleophile and base.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100123"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X23000296/pdfft?md5=82ef7ca038a6e502846afff04ea64b3c&pid=1-s2.0-S2665928X23000296-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of Plasmodium falciparum plasmepsins by drugs targeting HIV-1 protease: A way forward for antimalarial drug discovery 靶向 HIV-1 蛋白酶的药物对恶性疟原虫浆蛋白酶的抑制作用：抗疟药物研发的前进之路

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100128

Vandana Mishra , Anuradha Deshmukh , Ishan Rathore , Satadru Chakraborty , Swati Patankar , Alla Gustchina , Alexander Wlodawer , Rickey Y. Yada , Prasenjit Bhaumik

{"title":"Inhibition of Plasmodium falciparum plasmepsins by drugs targeting HIV-1 protease: A way forward for antimalarial drug discovery","authors":"Vandana Mishra , Anuradha Deshmukh , Ishan Rathore , Satadru Chakraborty , Swati Patankar , Alla Gustchina , Alexander Wlodawer , Rickey Y. Yada , Prasenjit Bhaumik","doi":"10.1016/j.crstbi.2024.100128","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100128","url":null,"abstract":"<div><p><em>Plasmodium</em> species are causative agents of malaria, a disease that is a serious global health concern. FDA-approved HIV-1 protease inhibitors (HIV-1 PIs) have been reported to be effective in reducing the infection by <em>Plasmodium</em> parasites in the population co-infected with both HIV-1 and malaria. However, the mechanism of HIV-1 PIs in mitigating <em>Plasmodium</em> pathogenesis during malaria/HIV-1 co-infection is not fully understood. In this study we demonstrate that HIV-1 drugs ritonavir (RTV) and lopinavir (LPV) exhibit the highest inhibition activity against plasmepsin II (PMII) and plasmepsin X (PMX) of <em>P. falciparum.</em> Crystal structures of the complexes of PMII with both drugs have been determined. The inhibitors interact with PMII <em>via</em> multiple hydrogen bonding and hydrophobic interactions. The P4 moiety of RTV forms additional interactions compared to LPV and exhibits conformational flexibility in a large S4 pocket of PMII. Our study is also the first to report inhibition of <em>P. falciparum</em> PMX by RTV and the mode of binding of the drug to the PMX active site. Analysis of the crystal structures implies that PMs can accommodate bulkier groups of these inhibitors in their S4 binding pockets. Structurally similar active sites of different vacuolar and non-vacuolar PMs suggest the potential of HIV-1 PIs in targeting these enzymes with differential affinities. Our structural investigations and biochemical data emphasize PMs as crucial targets for repurposing HIV-1 PIs as antimalarial drugs.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100128"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000059/pdfft?md5=38e95df2fe38c0df8f4ac91d7d0249de&pid=1-s2.0-S2665928X24000059-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139505362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Living in trinity of extremes: Genomic and proteomic signatures of halophilic, thermophilic, and pH adaptation 生活在三位一体的极端环境中：嗜卤、嗜热和酸碱度适应的基因组和蛋白质组特征

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100129

Aidana Amangeldina , Zhen Wah Tan , Igor N. Berezovsky

{"title":"Living in trinity of extremes: Genomic and proteomic signatures of halophilic, thermophilic, and pH adaptation","authors":"Aidana Amangeldina , Zhen Wah Tan , Igor N. Berezovsky","doi":"10.1016/j.crstbi.2024.100129","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100129","url":null,"abstract":"<div><p>Since nucleic acids and proteins of unicellular prokaryotes are directly exposed to extreme environmental conditions, it is possible to explore the genomic-proteomic compositional determinants of molecular mechanisms of adaptation developed by them in response to harsh environmental conditions. Using a wealth of currently available complete genomes/proteomes we were able to explore signatures of adaptation to three environmental factors, pH, salinity, and temperature, observing major trends in compositions of their nucleic acids and proteins. We derived predictors of thermostability, halophilic, and pH adaptations and complemented them by the principal components analysis. We observed a clear difference between thermophilic and salinity/pH adaptations, whereas latter invoke seemingly overlapping mechanisms. The genome-proteome compositional trade-off reveals an intricate balance between the work of base paring and base stacking in stabilization of coding DNA and r/tRNAs, and, at the same time, universal requirements for the stability and foldability of proteins regardless of the nucleotide biases. Nevertheless, we still found hidden fingerprints of ancient evolutionary connections between the nucleotide and amino acid compositions indicating their emergence, mutual evolution, and adjustment. The evolutionary perspective on the adaptation mechanisms is further studied here by means of the comparative analysis of genomic/proteomic traits of archaeal and bacterial species. The overall picture of genomic/proteomic signals of adaptation obtained here provides a foundation for future engineering and design of functional biomolecules resistant to harsh environments.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100129"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000060/pdfft?md5=6db45050bbde9f78ac6d75eb6e876f66&pid=1-s2.0-S2665928X24000060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Guide to serial synchrotron crystallography 系列同步加速器晶体学指南

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100131

Ki Hyun Nam

引用次数: 0

Doxorubicin catalyses self-assembly of p53 by phase separation 多柔比星通过相分离催化 p53 的自组装

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100133

Ankush Garg , Gaurav Kumar , Varinder Singh , Sharmistha Sinha

{"title":"Doxorubicin catalyses self-assembly of p53 by phase separation","authors":"Ankush Garg , Gaurav Kumar , Varinder Singh , Sharmistha Sinha","doi":"10.1016/j.crstbi.2024.100133","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100133","url":null,"abstract":"<div><p>Liquid-liquid phase separation plays a crucial role in cellular physiology, as it leads to the formation of membrane-less organelles in response to various internal stimuli, contributing to various cellular functions. However, the influence of exogenous stimuli on this process in the context of disease intervention remains unexplored. In this current investigation, we explore the impact of doxorubicin on the abnormal self-assembly of p53 using a combination of biophysical and imaging techniques. Additionally, we shed light on the potential mechanisms behind chemoresistance in cancer cells carrying mutant p53.</p><p>Our findings reveal that doxorubicin co-localizes with both wild-type p53 (WTp53) and its mutant variants. Our <em>in vitro</em> experiments indicate that doxorubicin interacts with the N-terminal-deleted form of WTp53 (WTp53ΔNterm), inducing liquid-liquid phase separation, ultimately leading to protein aggregation. Notably, the p53 variants at the R273 position exhibit a propensity for phase separation even in the absence of doxorubicin, highlighting the destabilizing effects of point mutations at this position.</p><p>The strong interaction between doxorubicin and p53 variants, along with its localization within the protein condensates, provides a potential explanation for the development of chemotherapy resistance. Collectively, our cellular and <em>in vitro</em> studies emphasize the role of exogenous agents in driving phase separation-mediated p53 aggregation.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100133"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000102/pdfft?md5=42fe7a839b8535990a75792d8a30bcc4&pid=1-s2.0-S2665928X24000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139936977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0