Proteins-Structure Function and Bioinformatics最新文献_第5页

Distribution of Polyphosphate Kinase 2 Genes in Bacteria Underscores a Dynamic Evolutionary History. 多磷酸激酶 2 基因在细菌中的分布证明了动态进化的历史

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-18 DOI: 10.1002/prot.26780

Ryusei Matsumoto, Tomoaki Matsuura, Liam M Longo

{"title":"Distribution of Polyphosphate Kinase 2 Genes in Bacteria Underscores a Dynamic Evolutionary History.","authors":"Ryusei Matsumoto, Tomoaki Matsuura, Liam M Longo","doi":"10.1002/prot.26780","DOIUrl":"10.1002/prot.26780","url":null,"abstract":"Polyphosphate kinase 2 (PPK2) enzymes catalyze phosphoryl transfer from polyphosphate to nucleotides and are divided into three classes, each presumed to have different catalytic preferences. With relevance to biotechnology, medicine, and primitive biology, there is significant interest in understanding the evolutionary history of PPK2 enzymes and predicting their functional properties. We reasoned that the distribution and pairing preferences of PPK2 gene classes across the prokaryote tree of life may shed light on these questions. PPK2 was found to be a dynamic gene family, often present in only a subset of species within a clade, even when considering a single genus. Although all possible PPK2 pairs were observed, a ~2-fold enrichment for Class I enzymes in species with multiple PPK2 genes strongly shapes pairing preferences. PPK2 class preference in the absence of PPK1, which synthesizes rather than utilizes polyphosphate, indicates the potential for functional adaptation and/or promiscuity with respect to reaction directionality for all classes, a feature that has previously been associated only with Class I. Patterns of adjacent PPK2 genes revealed signatures of gene duplication, as adjacent genes overwhelmingly belonged to the same class, as well as the potential for an added layer of PPK2 dynamics: hetero-oligomerization of single-domain Class II enzymes to recapitulate the structure of two-domain Class II enzymes. Finally, an updated PPK2 tree constructed from domains instead of genes calls into question established narratives of PPK2 evolution, putting new limits on the extent to which nucleobase promiscuity can be invoked in the early evolution of this family.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"972-980"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848566","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 Insights Into the Impact of the Glycine-Rich Loop Mutation in Noonan Syndrome on the ATP Binding Pocket of CRAF Kinase. Noonan综合征中富含甘氨酸环突变对CRAF激酶ATP结合袋影响的结构见解。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-30 DOI: 10.1002/prot.26769

Fatemeh Janati-Fard, Mohammad R Housaindokht, Fatemeh Moosavi, Saeideh Nakhaei-Rad

{"title":"Structural Insights Into the Impact of the Glycine-Rich Loop Mutation in Noonan Syndrome on the ATP Binding Pocket of CRAF Kinase.","authors":"Fatemeh Janati-Fard, Mohammad R Housaindokht, Fatemeh Moosavi, Saeideh Nakhaei-Rad","doi":"10.1002/prot.26769","DOIUrl":"10.1002/prot.26769","url":null,"abstract":"The pathogenic G361A variant of CRAF, associated with increased intrinsic kinase activity in Noonan syndrome (NS), remains poorly understood in terms of its molecular and structural impact on kinase activity. To elucidate the mechanistic implications of the glycine to alanine substitution at residue 361 in CRAF, we employed molecular dynamics simulations. Our findings reveal that this mutation predominantly affects the ATP binding pocket and critical intermolecular interactions within the active cleft that favors the phosphate transfer reaction. Notably, our data highlight significant alterations in key interactions involving Lys470/Asp486 and ATP.Mg2+ in CRAFG361A that are absent in wild-type CRAF. Additionally, we identified a novel interaction mode between Lys431 and γ-phosphate in wild-type CRAF, a residue evolutionarily conserved in CRAFs but not in related kinases such as BRAF, ARAF, and KSR1/2. Furthermore, observed shifts in the αC-helix and G-loop relative to the wild-type correlate with an enlarged ATP-binding cavity in the mutant, reflecting structural adaptations due to these mutations. Overall, these structural insights underscore the elevated intrinsic kinase activity of the CRAFG361A variant and provide crucial mechanistic details that could inform the development of specific inhibitors targeting this variant.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1022-1034"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911210","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

Cryo-EM Structure of Human Hyaluronidase PH-20. 人透明质酸酶PH-20的低温电镜结构。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-25 DOI: 10.1002/prot.26788

Seong-Bin Im, Hyung Nam Song, Tae-Kyeong Jeong, Nayun Kim, Kyuwan Kim, Soon-Jae Park, Byung-Ha Oh

引用次数: 0

Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (Pf Grp94). 恶性疟原虫葡萄糖调节蛋白94kda （PfGrp94）伴侣蛋白功能的表征及抑制

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-13 DOI: 10.1002/prot.26779

Florence Lisa Muzenda, Melissa Louise Stofberg, Wendy Mthembu, Ikechukwu Achilonu, Erick Strauss, Tawanda Zininga

{"title":"Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (Pf Grp94).","authors":"Florence Lisa Muzenda, Melissa Louise Stofberg, Wendy Mthembu, Ikechukwu Achilonu, Erick Strauss, Tawanda Zininga","doi":"10.1002/prot.26779","DOIUrl":"10.1002/prot.26779","url":null,"abstract":"Plasmodium falciparum expresses four heat shock protein 90 (Hsp90) members. Among these, one, glucose-regulated protein 94 (PfGrp94), is localized in the endoplasmic reticulum (ER). Both the cytosolic and ER-based Hsp90s are essential for parasite survival under all growth conditions. The cytosolic version has been extensively studied and has been targeted in several efforts through the repurposing of anticancer therapeutics as antimalarial drugs. However, PfGrp94 has not been fully characterized and some of its functions related to the ER stress response are not fully understood. Structural analysis of the recombinant full-length PfGrp94 protein showed a predominantly α-helical secondary structure and its thermal resilience was modulated by 5'-N-ethyl-carboxamide-adenosine (NECA) and nucleotides ATP/ADP. PfGrp94 exhibits ATPase activity and suppressed heat-induced aggregation of a model substrate, malate dehydrogenase, in a nucleotide-dependent manner. However, these PfGrp94 chaperone functions were abrogated by NECA. Molecular docking and molecular dynamics (MD) simulations showed that NECA interacted with unique residues on PfGrp94, which could be potentially exploited for selective drug design. Finally, using parasites maintained at the red blood stage, NECA exhibited moderate antiplasmodial activity (IC50 of 4.3, 7.4, and 10.0 μM) against three different P. falciparum strains. Findings from this study provide the first direct evidence for the correlation between in silico, biochemical, and in vitro data toward utilizing the ER-based chaperone, PfGrp94, as a drug target against the malaria parasites.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"957-971"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820242","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

SUPERMAGO: Protein Function Prediction Based on Transformer Embeddings. 基于变压器嵌入的蛋白质功能预测。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-22 DOI: 10.1002/prot.26782

Gabriel Bianchin de Oliveira, Helio Pedrini, Zanoni Dias

{"title":"SUPERMAGO: Protein Function Prediction Based on Transformer Embeddings.","authors":"Gabriel Bianchin de Oliveira, Helio Pedrini, Zanoni Dias","doi":"10.1002/prot.26782","DOIUrl":"10.1002/prot.26782","url":null,"abstract":"Recent technological advancements have enabled the experimental determination of amino acid sequences for numerous proteins. However, analyzing protein functions, which is essential for understanding their roles within cells, remains a challenging task due to the associated costs and time constraints. To address this challenge, various computational approaches have been proposed to aid in the categorization of protein functions, mainly utilizing amino acid sequences. In this study, we introduce SUPERMAGO, a method that leverages amino acid sequences to predict protein functions. Our approach employs Transformer architectures, pre-trained on protein data, to extract features from the sequences. We use multilayer perceptrons for classification and a stacking neural network to aggregate the predictions, which significantly enhances the performance of our method. We also present SUPERMAGO+, an ensemble of SUPERMAGO and DIAMOND, based on neural networks that assign different weights to each term, offering a novel weighting mechanism compared with existing methods in the literature. Additionally, we introduce SUPERMAGO+Web, a web server-compatible version of SUPERMAGO+ designed to operate with reduced computational resources. Both SUPERMAGO and SUPERMAGO+ consistently outperformed state-of-the-art approaches in our evaluations, establishing them as leading methods for this task when considering only amino acid sequence information.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"981-996"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878570","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

Structural Basis for Monomer-Dimer Transition of Dri1 Upon Heme Binding. 血红素结合时 Dri1 单体-二聚体转变的结构基础

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-13 DOI: 10.1002/prot.26778

Xiao-Ying Wang, Jing Zhang, Hong-Yan Li, Chen-Song Dong, Huai-En Dai, Mingzhu Wang, Lin Liu

引用次数: 0

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-26 DOI: 10.1002/prot.26785

Matthias Fellner, George Randall, Ianah R C G Bitac, Annmaree K Warrender, Ashish Sethi, Raz Jelinek, Itamar Kass

{"title":"Similar but Distinct-Biochemical Characterization of the Staphylococcus aureus Serine Hydrolases FphH and FphI.","authors":"Matthias Fellner, George Randall, Ianah R C G Bitac, Annmaree K Warrender, Ashish Sethi, Raz Jelinek, Itamar Kass","doi":"10.1002/prot.26785","DOIUrl":"10.1002/prot.26785","url":null,"abstract":"Staphylococcus aureus is a major cause of infections like bacteremia, pneumonia, and endocarditis. These infections are often linked to the ability of S. aureus to form biofilms. Several S. aureus serine hydrolases have previously been identified to be active during biofilm-forming conditions. Here, we present the biochemical characterization of two of these enzymes-fluorophosphonate binding hydrolase H and I (FphH, FphI). Cryogenic and room-temperature X-ray crystallography, enzymatic substrate profiling, small-angle X-ray scattering analysis, and molecular dynamics simulations provide new insights into similarities and differences between these two hydrolase_4 domain family members. We discover that these enzymes share an overall fold, including a flexible lid or cap region above the active site, which can be seen to be mobile in solution. Differences in the active site pocket and lid residues differentiate them and explain speed differences in their carboxyesterase substrate profile toward small unbranched carbon chain ester molecules. The first analysis of FphI is also compared to our previous knowledge of FphH and its association to stress conditions. These results enable the future precise targeting of Fph serine hydrolase family members with a long-term goal to significantly improve the health and wellbeing of individuals and populations worldwide.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1009-1021"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900932","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

Role of Mutual Information Profile Shifts in Assessing the Pathogenicity of Mutations on Protein Functions: The Case of Pyrin Variants Associated With Familial Mediterranean Fever. 互信息谱变化在评估蛋白质功能突变致病性中的作用：与家族性地中海热相关的Pyrin变异的案例

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-31 DOI: 10.1002/prot.26795

Aysima Hacisuleyman, Ahmet Gul, Burak Erman

{"title":"Role of Mutual Information Profile Shifts in Assessing the Pathogenicity of Mutations on Protein Functions: The Case of Pyrin Variants Associated With Familial Mediterranean Fever.","authors":"Aysima Hacisuleyman, Ahmet Gul, Burak Erman","doi":"10.1002/prot.26795","DOIUrl":"10.1002/prot.26795","url":null,"abstract":"This study presents a novel method to assess the pathogenicity of pyrin protein mutations by using mutual information (MI) as a measure to quantify the correlation between residue motions or fluctuations and associated changes affecting the phenotype. The concept of MI profile shift is presented to quantify changes in MI upon mutation, revealing insights into residue-residue interactions at critical positions. We apply this method to the pyrin protein variants, which are associated with an autosomal recessively inherited disease called familial Mediterranean fever (FMF) since the available tools do not help predict the pathogenicity of the most penetrant variants. We demonstrate the utility of MI profile shifts in assessing the effects of mutations on protein stability, function, and disease phenotype. The importance of MI shifts, particularly the negative shifts observed in the pyrin example, as indicators of severe functional effects is emphasized. Additionally, the exploration of potential compensatory mechanisms suggested by positive MI shifts, which are otherwise random and inconsequential, is highlighted. The study also discusses challenges in relating MI profile changes to disease severity and advocates for comprehensive analysis considering genetic, environmental, and stochastic factors. Overall, this study provides insights into the molecular mechanisms underlying the pathogenesis of FMF and offers a framework for identifying potential therapeutic targets based on MI profile changes induced by mutations.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1035-1053"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911199","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

Correction to "Allosteric Modulation of Fluorescence Revealed by Hydrogen Bond Dynamics in a Genetically Encoded Maltose Biosensor". 修正“基因编码麦芽糖生物传感器中氢键动力学揭示的荧光变构调制”。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-20 DOI: 10.1002/prot.26787

引用次数: 0

Exploring Compactness and Dynamics of Apomyoglobin. 无肌红蛋白的致密性和动力学研究。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-05-01 Epub Date: 2024-12-23 DOI: 10.1002/prot.26786

Anna V Glyakina, Mariya Y Suvorina, Nikita V Dovidchenko, Natalya S Katina, Alexey K Surin, Oxana V Galzitskaya

{"title":"Exploring Compactness and Dynamics of Apomyoglobin.","authors":"Anna V Glyakina, Mariya Y Suvorina, Nikita V Dovidchenko, Natalya S Katina, Alexey K Surin, Oxana V Galzitskaya","doi":"10.1002/prot.26786","DOIUrl":"10.1002/prot.26786","url":null,"abstract":"Hydrogen-deuterium exchange mass spectrometry (HDX-MS) approach has become a valuable analytical complement to traditional methods. HDX-MS allows the identification of dynamic surfaces in proteins. We have shown that the introduction of various mutations into the amino acid sequence of whale apomyoglobin (apoMb) leads to a change in the number of exchangeable hydrogen atoms, which is associated with a change in its compactness in the native-like condition. Thus, amino acid substitutions V10A, A15S, P120G, and M131A result in an increase in the number of exchangeable hydrogen atoms at the native-like condition, while the mutant form A144S leads to a decrease in the number of exchangeable hydrogen atoms. This may be due to a decrease and increase in the compactness of apoMb structure compared to the wild-type apoMb, respectively. The L9F and L9E mutations did not affect the compactness of the molecule compared to the wild type. We have demonstrated that V10A and M131A substitutions lead to the maximum and large increase correspondently in the average number of exchangeable hydrogen atoms for deuterium, since these substitutions lead to the loss of contacts between important parts of myoglobin structure: helices A, G, and H, which are structured at the early stage of folding.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"997-1008"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878565","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