Proteins-Structure Function and Bioinformatics最新文献

Performance of Hybrid Strategies Combining MDockPP and AlphaFold2 in CAPRI Rounds 47-55.

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-04 DOI: 10.1002/prot.26805

Rui Duan, Xianjin Xu, Liming Qiu, Shuang Zhang, Xiaoqin Zou

引用次数: 0

DeepPhoPred: Accurate Deep Learning Model to Predict Microbial Phosphorylation. DeepPhoPred：预测微生物磷酸化的精确深度学习模型

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-09-06 DOI: 10.1002/prot.26734

Faisal Ahmed, Alok Sharma, Swakkhar Shatabda, Iman Dehzangi

{"title":"DeepPhoPred: Accurate Deep Learning Model to Predict Microbial Phosphorylation.","authors":"Faisal Ahmed, Alok Sharma, Swakkhar Shatabda, Iman Dehzangi","doi":"10.1002/prot.26734","DOIUrl":"10.1002/prot.26734","url":null,"abstract":"Phosphorylation is a substantial posttranslational modification of proteins that refers to adding a phosphate group to the amino acid side chain after translation process in the ribosome. It is vital to coordinate cellular functions, such as regulating metabolism, proliferation, apoptosis, subcellular trafficking, and other crucial physiological processes. Phosphorylation prediction in a microbial organism can assist in understanding pathogenesis and host-pathogen interaction, drug and antibody design, and antimicrobial agent development. Experimental methods for predicting phosphorylation sites are costly, slow, and tedious. Hence low-cost and high-speed computational approaches are highly desirable. This paper presents a new deep learning tool called DeepPhoPred for predicting microbial phospho-serine (pS), phospho-threonine (pT), and phospho-tyrosine (pY) sites. DeepPhoPred incorporates a two-headed convolutional neural network architecture with the squeeze and excitation blocks followed by fully connected layers that jointly learn significant features from the peptide's structural and evolutionary information to predict phosphorylation sites. Our empirical results demonstrate that DeepPhoPred significantly outperforms the existing microbial phosphorylation site predictors with its highly efficient deep-learning architecture. DeepPhoPred as a standalone predictor, all its source codes, and our employed datasets are publicly available at https://github.com/faisalahm3d/DeepPhoPred.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"465-481"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141867","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

Physicochemical Evaluation of Remote Homology in the Twilight Zone. 暮光之城中远程同源物的物理化学评估。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-09-01 DOI: 10.1002/prot.26742

Jamie Dennis Dixson, Rajeev Kumar Azad

{"title":"Physicochemical Evaluation of Remote Homology in the Twilight Zone.","authors":"Jamie Dennis Dixson, Rajeev Kumar Azad","doi":"10.1002/prot.26742","DOIUrl":"10.1002/prot.26742","url":null,"abstract":"A fundamental problem in the field of protein evolutionary biology is determining the degree and nature of evolutionary relatedness among homologous proteins that have diverged to a point where they share less than 30% amino acid identity yet retain similar structures and/or functions. Such proteins are said to lie within the \"Twilight Zone\" of amino acid identity. Many researchers have leveraged experimentally determined structures in the quest to classify proteins in the Twilight Zone. Such endeavors can be highly time consuming and prohibitively expensive for large-scale analyses. Motivated by this problem, here we use molecular weight-hydrophobicity physicochemical dynamic time warping (MWHP DTW) to quantify similarity of simulated and real-world homologous protein domains. MWHP DTW is a physicochemical method requiring only the amino acid sequence to quantify similarity of related proteins and is particularly useful in determining similarity within the Twilight Zone due to its resilience to primary sequence substitution saturation. This is a step forward in determination of the relatedness among Twilight Zone proteins and most notably allows for the discrimination of random similarity and true homology in the 0%-20% identity range. This method was previously presented expeditiously just after the outbreak of COVID-19 because it was able to functionally cluster ACE2-binding betacoronavirus receptor binding domains (RBDs), a task that has been elusive using standard techniques. Here we show that one reason that MWHP DTW is an effective technique for comparisons within the Twilight Zone is because it can uncover hidden homology by exploiting physicochemical conservation, a problem that protein sequence alignment algorithms are inherently incapable of addressing within the Twilight Zone. Further, we present an extended definition of the Twilight Zone that incorporates the dynamic relationship between structural, physicochemical, and sequence-based metrics.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"452-464"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115478","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

Valacyclovir and Acyclovir Are Substrates of the Guanine Deaminase Cytosolic PSD-95 Interactor (Cypin). 伐昔洛韦和阿昔洛韦是鸟嘌呤脱氨酶细胞质 PSD-95 互作因子 (Cypin) 的底物

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-08-29 DOI: 10.1002/prot.26740

Keith R Lange, Noor Rasheed, Xiaoyang Su, M Elena Diaz-Rubio, Bonnie L Firestein

{"title":"Valacyclovir and Acyclovir Are Substrates of the Guanine Deaminase Cytosolic PSD-95 Interactor (Cypin).","authors":"Keith R Lange, Noor Rasheed, Xiaoyang Su, M Elena Diaz-Rubio, Bonnie L Firestein","doi":"10.1002/prot.26740","DOIUrl":"10.1002/prot.26740","url":null,"abstract":"Valacyclovir, enzymatically hydrolyzed in the body to acyclovir, is a guanine-based nucleoside analog commonly prescribed as an antiviral therapy. Previous reports suggest that guanosine analogs bind to guanine deaminase; however, it is unclear whether they act as inhibitors or substrates. Data from our laboratory suggest that inhibition of guanine deaminase by small molecules attenuates spinal cord injury-induced neuropathic pain. Here, we examine whether the guanosine analogs valacyclovir and acyclovir are deaminated by cypin (cytosolic PSD-95 interactor), the major guanine deaminase in the body, or if they act as cypin inhibitors. Using purified Rattus norvegicus cypin, we use NADH-coupled assay to confirm deamination of valacyclovir and determined Michaelis-Menten constants. Subsequently, we use tryptophan fluorescence quenching assay to calculate dissociation constants for valacyclovir and acyclovir and find that inclusion of the valine motif in valacyclovir increases affinity for cypin compared to acyclovir. To our knowledge, neither K m nor K D values for cypin has been previously reported for either compound. We use Amplex Red assay and demonstrate that both valacyclovir and acyclovir are cypin substrates and that their metabolites are further processed by xanthine oxidase and uricase. Using molecular dynamics simulations, we demonstrate that an alpha helix near the active site is displaced when valacyclovir binds to cypin. Furthermore, we used LC-MS-based assay to directly confirm deamination of valacyclovir by cypin. Taken together, our results demonstrate a novel role for cypin in deamination of valacyclovir and acyclovir and suggest that therapeutics based on purine structures may be inactivated by cypin, decreasing inhibitory efficacy.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"430-440"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115479","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 and Biochemical Characterization of Aminoglycoside Nucleotidyltransferase(6)-Ib From Campylobacter fetus subsp. fetus. 胎儿弯曲杆菌亚种氨基糖苷核苷酸转移酶（6）-Ib 的结构和生化特性分析

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-09-09 DOI: 10.1002/prot.26745

Pranav Nalam, Paul D Cook, Brian A Smith

{"title":"Structural and Biochemical Characterization of Aminoglycoside Nucleotidyltransferase(6)-Ib From Campylobacter fetus subsp. fetus.","authors":"Pranav Nalam, Paul D Cook, Brian A Smith","doi":"10.1002/prot.26745","DOIUrl":"10.1002/prot.26745","url":null,"abstract":"Aminoglycoside antibiotics have played a critical role in the treatment of both Gram-negative and Gram-positive bacterial infections. However, antibiotic resistance has severely compromised the efficacy of aminoglycosides. A leading cause of aminoglycoside resistance is mediated by bacterial enzymes that inactivate these drugs via chemical modification. Aminoglycoside nucleotidyltransferase-6 (ANT(6)) enzymes inactivate streptomycin by transferring an adenyl group from ATP to position 6 on the antibiotic. Despite the clinical significance of this activity, ANT(6) enzymes remain relatively uncharacterized. Here, we report the first high resolution x-ray crystallographic structure of ANT(6)-Ib from Campylobacter fetus subsp. fetus bound with streptomycin. Structural modeling and gel filtration chromatography experiments suggest that the enzyme exists as a dimer in which both subunits contribute to the active site. Moreover, superposition of the ANT(6)-Ib structure with the structurally related enzyme lincosamide nucleotidyltransferase B (LinB) permitted the identification of a putative nucleotide binding site. These data also suggest that residues D44 and D46 coordinate essential divalent metal ions and D102 functions as the catalytic base.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"413-419"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156778","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

Molecular Interactions of the Pioneer Transcription Factor GATA3 With DNA. 先锋转录因子 GATA3 与 DNA 的分子相互作用

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-09-24 DOI: 10.1002/prot.26749

Sowmomita Gharui, Durba Sengupta

{"title":"Molecular Interactions of the Pioneer Transcription Factor GATA3 With DNA.","authors":"Sowmomita Gharui, Durba Sengupta","doi":"10.1002/prot.26749","DOIUrl":"10.1002/prot.26749","url":null,"abstract":"The GATA3 transcription factor is a pioneer transcription factor that is critical in the development, proliferation, and maintenance of several immune cell types. Identifying the detailed conformational dynamics and interactions of this transcription factor, as well as its clinically important population variants will allow us to unravel its mode of action. In this study, we analyze the molecular interactions of the GATA3 transcription factor bound to dsDNA as well as three clinically important population variants by atomistic molecular dynamics simulations. We identify the effect of the variants on the DNA conformational dynamics and delineate the differences compared to the wildtype transcription factor that could be related to impaired function. We highlight the structural plasticity in the binding of the GATA3 transcription factor and identify important DNA-protein contacts. Although the DNA-protein contacts are persistent and appear to be stable, they exhibit nanosecond timescale fluctuations and several binding/unbinding events. Further, we identify differential DNA binding in the three variants and show that the N-terminal binding is reduced in two of the variants. Our results indicate that reduced minor groove width and DNA diameter are important hallmarks for the binding of GATA3. Our work is an important step towards understanding the functional dynamics of the GATA3 protein and its clinically significant population variants.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"555-566"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309208","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 Insight Into the Function of DnaB Helicase in Bacterial DNA Replication. 从结构上揭示 DnaB 螺旋酶在细菌 DNA 复制中的功能

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-09-04 DOI: 10.1002/prot.26746

Zhiming Zhang, Jiang Chen, Maochun Yao, Ganggang Wang

引用次数: 0

The High-Affinity Chymotrypsin Inhibitor Eglin C Poorly Inhibits Human Chymotrypsin-Like Protease: Gln192 and Lys218 Are Key Determinants. 高亲和力糜蛋白酶抑制剂 Eglin C 对人类糜蛋白酶样蛋白酶的抑制效果很差：Gln192和Lys218是关键的决定因素

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-09-20 DOI: 10.1002/prot.26750

Bálint Zoltán Németh, Bence Kiss, Miklós Sahin-Tóth, Csaba Magyar, Gábor Pál

引用次数: 0

A Novel Tetravalent CD95/Fas Fusion Protein With Superior CD95L/FasL Antagonism. 一种新型四价 CD95/Fas 融合蛋白，具有卓越的 CD95L/FasL 拮抗作用。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-02-01 Epub Date: 2024-09-01 DOI: 10.1002/prot.26741

Isabell Lang, Oliver Paulus, Olena Zaitseva, Harald Wajant

{"title":"A Novel Tetravalent CD95/Fas Fusion Protein With Superior CD95L/FasL Antagonism.","authors":"Isabell Lang, Oliver Paulus, Olena Zaitseva, Harald Wajant","doi":"10.1002/prot.26741","DOIUrl":"10.1002/prot.26741","url":null,"abstract":"Inhibition of CD95/Fas activation is currently under clinical investigation as a therapy for glioblastoma multiforme and preclinical studies suggest that disruption of the CD95-CD95L interaction could also be a strategy to treat inflammatory and neurodegenerative disorders. Besides neutralizing anti-CD95L/FasL antibodies, mainly CD95ed-Fc, a dimeric Fc fusion protein of the extracellular domain of CD95 (CD95ed), is used to prevent CD95 activation. In view of the fact that full CD95 activation requires CD95L-induced CD95 trimerization and clustering of the resulting liganded CD95 trimers, we investigated whether fusion proteins of the extracellular domain of CD95 with a higher valency than CD95ed-Fc have an improved CD95L-neutralization capacity. We evaluated an IgG1(N297A)-based tetravalent CD95ed fusion protein which was obtained by replacing the variable domains of IgG1(N297A) with CD95ed (CD95ed-IgG1(N297A)) and a hexavalent variant obtained by fusion of CD95ed with a TNC-Fc(DANA) scaffold (CD95ed-TNC-Fc(DANA)) promoting hexamerization. The established N297A and DANA mutations were used to minimize FcγR binding of the constructs under maintenance of neonatal Fc receptor (FcRn) binding. Size exclusion high-performance liquid chromatography indicated effective assembly of CD95ed-IgG1(N297A). More important, CD95ed-IgG1(N297A) was much more efficient than CD95ed-Fc in protecting cells from cell death induction by human and murine CD95L. Surprisingly, despite its hexavalent structure, CD95ed-TNC-Fc(DANA) displayed an at best minor improvement of the capacity to neutralize CD95L suggesting that besides valency, other factors, such as spatial organization and agility of the CD95ed domains, play also a role in neutralization of CD95L trimers by CD95ed fusion proteins. More studies are now required to evaluate the superior CD95L-neutralizing capacity of CD95ed-IgG1(N297A) in vivo.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"441-451"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115465","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

Correction to Rigidifying Flexible Sites: A Promising Strategy to Improve Thermostability of Lysophospholipase From Pyrococcus abyssi.

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-01-31 DOI: 10.1002/prot.26804

引用次数: 0