Proteins-Structure Function and Bioinformatics最新文献_第9页

Structural and Enzymological Characterization of Phosphoserine Phosphatase From Brucella melitensis. 梅利特布鲁氏菌磷酸丝氨酸磷酸酶的结构与酶学特性研究。

IF 2.8 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-28 DOI: 10.1002/prot.70027

Tanguy Scaillet, Élise Pierson, Marianne Fillet, Johan Wouters

{"title":"Structural and Enzymological Characterization of Phosphoserine Phosphatase From Brucella melitensis.","authors":"Tanguy Scaillet, Élise Pierson, Marianne Fillet, Johan Wouters","doi":"10.1002/prot.70027","DOIUrl":"https://doi.org/10.1002/prot.70027","url":null,"abstract":"Amino acid L-serine (L-Ser) is a precursor of various biomolecules, including other amino acids, glutathione, and nucleotides. The metabolism of this amino acid is crucial in diseases such as brucellosis. Previous studies have revealed that the enzymes involved in L-Ser biosynthesis are essential for Brucella replication, making them potential targets for the development of new drugs. Here, we focus on Brucella melitensis phosphoserine phosphatase (BmPSP), which catalyzes the dephosphorylation of phosphoserine in L-Ser. The enzyme is characterized through enzymatic and structural studies, leading to the discovery of its first crystallographic structures. The interactions of BmPSP with different ligands are also investigated. We demonstrate that the substitution of its Mg2+ cofactor with Ca2+ inhibits the enzyme and results in a slight movement of catalytic residues in the active site. Crystallographic structures of BmPSP in complex with substrate, reaction products, and substrate analogs are also detailed, revealing the interaction between these molecules and the active site residues. This structural study provides a better understanding of phosphoserine phosphatases, highlighting the involvement of two highly conserved residues in the mechanism of substrate entry into the active site.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735758","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

The Crystal Structure of Human Transport and Golgi Organization 2 Homolog (TANGO2) Protein Reveals an αββα-Fold Arrangement. 人体运输和高尔基组织2同源蛋白（TANGO2）的晶体结构显示αββα-折叠排列。

IF 2.8 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-28 DOI: 10.1002/prot.70023

Anne Cooper, Alyssa Powers, Kevin P Battaile, Al-Walid Mohsen, David K Johnson, Scott Lovell, Lina Ghaloul-Gonzalez

{"title":"The Crystal Structure of Human Transport and Golgi Organization 2 Homolog (TANGO2) Protein Reveals an αββα-Fold Arrangement.","authors":"Anne Cooper, Alyssa Powers, Kevin P Battaile, Al-Walid Mohsen, David K Johnson, Scott Lovell, Lina Ghaloul-Gonzalez","doi":"10.1002/prot.70023","DOIUrl":"10.1002/prot.70023","url":null,"abstract":"Transport and Golgi Organization 2 Homolog (TANGO2) protein deficiency disorder (TDD) is a rare autosomal recessive disorder characterized by multi-systemic abnormalities and significant phenotypic variability including neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, rhabdomyolysis, life-threatening metabolic derangements, and cardiac arrhythmias. Mutations in TANGO2 result in mitochondrial dysfunction, abnormal lipid homeostasis with cardiolipin deficiency, and impaired Golgi-ER trafficking in TANGO2 patient-derived cells. Despite the wide recognition of the clinical manifestations of TDD and numerous molecular studies, the precise function of TANGO2 and the pathophysiology of TDD remain poorly understood. A computationally derived three-dimensional structure model suggested that TANGO2 adopts an αββα-fold, similar to the N-terminal nucleophile aminohydrolase (Ntn) superfamily of proteins, but the experimentally verified structure has not been available thus far. Here, we present the first crystal structure of the recombinant human TANGO2, determined at 1.70 Å resolution. The X-ray structure data confirmed its predicted tertiary fold with similarity to the Ntn-hydrolase family of proteins, and the comparative analysis of the active site architecture, including residues involved in catalysis and putative ligand binding site, suggests a potential hydrolase function. Additional examination of the common mutation sites found in TDD patients provides insight regarding their potential effect on protein structure integrity.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735759","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

Responses to Ligand Binding in the Bacterial DNA Sliding Clamp "β-Clamp" Manifest in Dynamic Allosteric Effects. 细菌DNA滑动钳“β-钳”对配体结合的响应表现为动态变构效应。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-26 DOI: 10.1002/prot.70024

Signe Simonsen, Andreas Prestel, Eva C Østerlund, Marit Otterlei, Thomas J D Jørgensen, Birthe B Kragelund

{"title":"Responses to Ligand Binding in the Bacterial DNA Sliding Clamp \"β-Clamp\" Manifest in Dynamic Allosteric Effects.","authors":"Signe Simonsen, Andreas Prestel, Eva C Østerlund, Marit Otterlei, Thomas J D Jørgensen, Birthe B Kragelund","doi":"10.1002/prot.70024","DOIUrl":"https://doi.org/10.1002/prot.70024","url":null,"abstract":"The homo-dimeric, ring-shaped bacterial DNA sliding clamp, β-clamp, is a central hub in DNA replication and repair. It interacts with a plethora of proteins via their short linear motifs, binding to the same hydrophobic binding pocket on β-clamp. Although the structure, functions, and interactions of β-clamp have been amply studied, less focus has been on understanding its dynamics and how this is influenced by ligand binding. In this work, we have made a backbone nuclear magnetic resonance (NMR) assignment of the 83 kDa dimeric β-clamp and used NMR in combination with hydrogen-deuterium exchange mass spectrometry to scrutinize the dynamics of β-clamp and how ligand binding affects this. We found that the binding of a short peptide from the polymerase III α subunit affects the dynamics and stability of β-clamp. The effect not only appears locally around the binding pocket but also globally through dynamic allosteric connections to distant regions of the protein, including the dimer interface. The dissipated dynamic effect from ligand binding is likely a consequence of a unique binding pocket architecture that connects distant parts of the structure and may reflect a mechanism of structural plasticity in protein hubs, where different ligands impose differential responses in the structure and dynamics of β-clamp, resulting in diverse functional responses.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719223","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 Variability of Pfam Domains Based on Alphafold2 Predictions. 基于Alphafold2预测的Pfam结构域结构变异性。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-22 DOI: 10.1002/prot.70021

Elly Poretsky, Carson M Andorf, Taner Z Sen

{"title":"Structural Variability of Pfam Domains Based on Alphafold2 Predictions.","authors":"Elly Poretsky, Carson M Andorf, Taner Z Sen","doi":"10.1002/prot.70021","DOIUrl":"https://doi.org/10.1002/prot.70021","url":null,"abstract":"Understanding the biological functions of proteins is one of the main goals of functional genomics. Such understanding will help control and manipulate biological processes to enhance desirable traits, including improved abiotic and biotic stress resistance in humans, animals, plants, and microbes. Protein domains, regarded as the functional building blocks of proteins, have been used extensively to predict protein function. Sequence-based approaches for protein function prediction, including the use of protein domain prediction from resources like the Pfam database, remain popular due to their reliability, low cost, and ease of use. Although the sequence variability of Pfam domains has been reported in several studies, their structural variability has been understudied. Here, we have extracted the Pfam domain structural portion from the predicted structures of the 16 model organism proteomes in the AlphaFold2 database. Our analysis revealed that many families contained between 20% and 40% members with no assigned regular secondary structures, demonstrating within-family structural variability. To better understand this structural variability, we used FoldSeek and agglomerative clustering to identify structural variability in Pfam families. We then analyzed specific cases to provide structural details for this variability. In this study, we have used two popular prediction applications/resources, Alphafold2 and Pfam, to demonstrate inherent variability in protein domain predictions by comparing their predicted structures. Our study shows that detection of structural variability in Pfam families can facilitate curation and refinement of Pfam families, while demonstrating the need to develop more accurate protein domain prediction workflows.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692585","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

The SIRT1 N-Terminal Domain as a Common Binding Interface for PPARγ Anchoring. SIRT1 n端结构域作为ppar - γ锚定的共同结合接口。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-17 DOI: 10.1002/prot.70022

Caique Camargo Malospirito, Gabriel Ernesto Jara, Víctor Ulian Antunes, Giovanna Blazutti Elias, Marieli Mariano Goncalves Dias, Fernanda Aparecida Heleno Batista, Paulo Sergio Lopes de Oliveira, Ana Carolina Migliorini Figueira

{"title":"The SIRT1 N-Terminal Domain as a Common Binding Interface for PPARγ Anchoring.","authors":"Caique Camargo Malospirito, Gabriel Ernesto Jara, Víctor Ulian Antunes, Giovanna Blazutti Elias, Marieli Mariano Goncalves Dias, Fernanda Aparecida Heleno Batista, Paulo Sergio Lopes de Oliveira, Ana Carolina Migliorini Figueira","doi":"10.1002/prot.70022","DOIUrl":"https://doi.org/10.1002/prot.70022","url":null,"abstract":"Insulin resistance, a global health threat linked to type 2 diabetes and obesity, can be addressed by modulating the activity of the Sirtuin 1 (SIRT1), a deacetylase that enhances insulin sensitivity by deacetylating the Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) at lysine 268 and 293. Understanding the binding interfaces between SIRT1 and PPARγ is critical to developing new strategies to combat insulin resistance. In this study, we present four experimentally supported binding models of SIRT1 with acetylated PPARγ: one at position 268 and three at position 293 (SIRT1-K268PPARγ and SIRT1-K293PPARγ1-3 models). These models were generated through an integration of in silico modeling and in vitro binding affinity assays. Our models revealed that the SIRT1:PPARγ binding interface is structured by SIRT1's 3-helix bundle in N-terminus domain (NTD(3HB)) and the catalytic domain (CD). The CD accommodated the acetylated peptide in its active site, while NTD(3HB) anchors PPARγ at a region between loops α1-β1 and α2'-α3 within PPARγ's ligand binding domain (LBD). Notably, the SIRT1-NTD(3HB) consistently bound to the same region of PPARγ in both models, highlighting a common mode for interaction. Through molecular dynamic simulation and binding assays, we demonstrated that either removal of SIRT1-NTD(3HB) or mutation within PPARγ-LBD significantly reduces binding affinity, underscoring the role of NTD(3HB) in substrate anchoring. Additionally, we provided evidence of SIRT1 dimerization, with substrate binding inducing its dissociation to form a heterodimer with PPARγ. These findings underscore the importance of the SIRT1 NTD(3HB) in PPARγ anchoring and offer insights into the activation mechanism of SIRT1, with potential implications for drug development targeting insulin resistance.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651294","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

Biomolecular Interaction Prediction in the Pre- and Post-AlphaFold Era: The 8th CAPRI Evaluation. 前和后alphafold时代的生物分子相互作用预测：第八次CAPRI评价。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-14 DOI: 10.1002/prot.70018

Marc F Lensink, Nessim Raouraoua, Guillaume Brysbaert, Sameer Velankar, Shoshana J Wodak, Alexandre M J J Bonvin

{"title":"Biomolecular Interaction Prediction in the Pre- and Post-AlphaFold Era: The 8th CAPRI Evaluation.","authors":"Marc F Lensink, Nessim Raouraoua, Guillaume Brysbaert, Sameer Velankar, Shoshana J Wodak, Alexandre M J J Bonvin","doi":"10.1002/prot.70018","DOIUrl":"https://doi.org/10.1002/prot.70018","url":null,"abstract":"We report on the 8th CAPRI Evaluation period, capturing the assessment of CAPRI Rounds 47 to 55 (excluding the CASP and COVID-related Rounds), which have witnessed the transition to AI-driven prediction tools such as AlphaFold and related alternatives. The prediction Rounds in this evaluation are characterized by a high level of difficulty due to various factors, including the nature of the targets, the intricacy of the interfaces to be predicted, and conformational changes. A total of 11 targets encompassing 21 interfaces, mostly in the difficult prediction category, were evaluated. While a retrospective analysis reveals a strong performance of AlphaFold on those targets, human predictors still outperform AI on difficult targets, particularly those involving antibodies and nucleic acids. Almost 25 years after its birth, CAPRI remains a vibrant and collaborative initiative with active participation from approximately 50 predictor and scorer groups and 10 servers. Continued contributions from experimentalists providing targets to such blind experiments, and further advances in AI, sampling strategies, and improvement in scoring methods will be key to overcoming remaining structural prediction challenges in complex biomolecular systems.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627859","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

Supervised Learning of Protein Melting Temperature: Cross-Species vs. Species-Specific Prediction. 蛋白质熔化温度的监督学习：跨物种vs物种特异性预测。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-14 DOI: 10.1002/prot.70019

Sebastián García López, Jesper Salomon, Wouter Boomsma

{"title":"Supervised Learning of Protein Melting Temperature: Cross-Species vs. Species-Specific Prediction.","authors":"Sebastián García López, Jesper Salomon, Wouter Boomsma","doi":"10.1002/prot.70019","DOIUrl":"https://doi.org/10.1002/prot.70019","url":null,"abstract":"Protein melting temperatures are important proxies for stability, and frequently probed in protein engineering campaigns, for instance for enzyme discovery and protein optimization. With the emergence of large datasets of melting temperatures for diverse natural proteins, it has become possible to train models to predict this quantity, and the literature has reported impressive performance values in terms of Spearman rho. The high correlation scores suggest that it should be possible to accurately predict melting temperature changes in engineered variants, and to reliably identify naturally thermostable proteins. However, in practice, results in these settings are often disappointing. In this paper, we explore this apparent discrepancy. We show that Spearman rho over cross-species data gives an overly optimistic impression of prediction performance, and that this metric reflects the ability to distinguish global differences in amino acid composition between species, rather than the specific effects of genetic variation. We proceed by investigating whether cross-species training on melting temperature is beneficial at all, compared to training specific models for each species. We address this question using four different transfer-learning approaches and a fine-tuning procedure. Surprisingly, we consistently find no benefit of cross-species training. We conclude that (1) current models for supervised prediction of melting temperature perform substantially worse than the literature suggests, and (2) that reliable transfer across species is still a challenging problem. An implementation of this work is available at https://github.com/deltadedirac/thermocontrast_tm.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627860","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 Mimicry Without Glyoxalase I Functional Convergence: A Homogentisate 1,2-Dioxygenase From Acinetobacter. 没有乙二醛酶的结构模拟I功能收敛：来自不动杆菌的均质1,2-双加氧酶。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-12 DOI: 10.1002/prot.70020

Pil-Won Seo, Seung-A Hwangbo, Jeong-Sun Kim, Suk-Youl Park

{"title":"Structural Mimicry Without Glyoxalase I Functional Convergence: A Homogentisate 1,2-Dioxygenase From Acinetobacter.","authors":"Pil-Won Seo, Seung-A Hwangbo, Jeong-Sun Kim, Suk-Youl Park","doi":"10.1002/prot.70020","DOIUrl":"https://doi.org/10.1002/prot.70020","url":null,"abstract":"Homogentisate 1,2-dioxygenase (HGD) is a non-heme iron enzyme that plays a crucial role in phenylalanine and tyrosine metabolism. Acinetobacter-derived HGD (AcHGD) exhibits structural similarity to glyoxalase I (GLO1) but lacks GLO1 activity. In this study, we analyzed the crystal structure of AcHGD at a resolution of 1.5 Å and investigated the molecular basis for its lack of GLO1 activity using enzymatic assays, isothermal titration calorimetry (ITC), and site-directed mutagenesis. Metal ion dependency assays revealed that AcHGD exhibits high specificity for Fe2+, supporting its role as a non-heme iron (II)-dependent dioxygenase. Structural analysis revealed that AcHGD adopts a β-barrel fold similar to GLO1 and coordinates Zn2+ through a 2-His-1-carboxylate facial triad. However, its substrate-binding tunnel is narrower than that of GLO1, preventing the binding of S-D-lactoylglutathione, the natural substrate of GLO1. Moreover, introducing GLO1-like mutations in the active site failed to confer GLO1 activity and instead abolished HGD activity. ITC analysis confirmed that AcHGD binds strongly to homogentisate but does not interact with S-D-lactoylglutathione. These findings demonstrate that despite its structural resemblance to GLO1, AcHGD lacks GLO1 activity due to differences in substrate specificity and active site architecture. This study provides insights into the structure-function relationship and evolutionary divergence between HGD and GLO1 enzymes.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621483","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

Predicting the Oligomeric State of Proteins Using Multiple Templates Detected by Complementary Alignment Methods. 利用互补比对方法检测多个模板预测蛋白质的寡聚状态。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-10 DOI: 10.1002/prot.70017

Yuxian Luo, Haiyan Wu, Hong Wei, Zhenling Peng, Jianyi Yang

{"title":"Predicting the Oligomeric State of Proteins Using Multiple Templates Detected by Complementary Alignment Methods.","authors":"Yuxian Luo, Haiyan Wu, Hong Wei, Zhenling Peng, Jianyi Yang","doi":"10.1002/prot.70017","DOIUrl":"https://doi.org/10.1002/prot.70017","url":null,"abstract":"Recognizing the oligomeric state of proteins is crucial for understanding the structure and function of proteins. In the CASP16 experiment, a two-stage prediction is proposed to challenge structure predictors, in which the oligomeric state is unknown at the first stage. The correct prediction of the oligomeric state plays a vital role in the subsequent step of structure prediction. To this end, we introduce POST, a new approach to the prediction of oligomeric state for homo-oligomers using multiple templates, specifically focusing on four states: monomer, dimer, trimer, and tetramer. POST employs three different algorithms, including dynamic programming, protein language model, and hidden Markov model, to detect homologous templates from an in-house template library (i.e., Q-BioLiP). These algorithms lead to three individual methods for oligomeric state prediction. Assessment on two independent datasets and 107 targets from CASP14 and CASP15 suggests that the templates detected by these methods are largely complementary. A combination of the templates from all individual methods results in the most accurate prediction. POST outperforms other sequence-based methods in predicting specific oligomeric states of proteins and distinguishing multimers from monomers, although it is inferior to other structure-based methods. Overall, POST is anticipated to be helpful in protein structure prediction and protein design.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610379","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

Three STEPs Forward: A Trio of Unexpected Structures of PTPN5. 三步进：PTPN5的三个意外结构。

IF 2.8 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-05 DOI: 10.1002/prot.70013

Liliana Guerrero, Ali Ebrahim, Blake T Riley, Sean H Kim, Anthony C Bishop, Jiaqian Wu, Ye Na Han, Lutz Tautz, Daniel A Keedy

{"title":"Three STEPs Forward: A Trio of Unexpected Structures of PTPN5.","authors":"Liliana Guerrero, Ali Ebrahim, Blake T Riley, Sean H Kim, Anthony C Bishop, Jiaqian Wu, Ye Na Han, Lutz Tautz, Daniel A Keedy","doi":"10.1002/prot.70013","DOIUrl":"10.1002/prot.70013","url":null,"abstract":"Protein tyrosine phosphatases (PTPs) play pivotal roles in myriad cellular processes by counteracting protein tyrosine kinases. Striatal-enriched protein tyrosine phosphatase (STEP, PTPN5) regulates synaptic function and neuronal plasticity in the brain and is a therapeutic target for several neurological disorders. Here, we present three new crystal structures of STEP, each with unexpected features. These include high-resolution conformational heterogeneity at multiple sites, a highly coordinated citrate molecule in the active site, a previously unseen conformational change at an allosteric site, an intramolecular disulfide bond that was characterized biochemically but had never been visualized structurally, and two serendipitous covalent ligand binding events at surface-exposed cysteines that are nearly or entirely unique to STEP among human PTPs. Together, our results offer new views of the conformational landscape of STEP that may inform structure-based design of allosteric small molecules to specifically inhibit this biomedically important enzyme.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568143","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