Structure最新文献_第3页

AI-guided cryo-EM analysis untangles uromodulin lattices that safeguard kidneys 人工智能引导的低温电镜分析解开了保护肾脏的尿调蛋白晶格

IF 5.7 2区生物学

Structure Pub Date : 2025-07-03 DOI: 10.1016/j.str.2025.06.003

Kelvin Han Chung Chong, Bin Wu

引用次数: 0

Decoding the molecular choreography of colibactin: Structural insights into a genotoxic assembly line 解码大肠杆菌蛋白的分子编排：基因毒性装配线的结构洞察

IF 5.7 2区生物学

Structure Pub Date : 2025-07-03 DOI: 10.1016/j.str.2025.06.001

Dandan Li, Zhijun Wang

引用次数: 0

Modeling phase separation of biomolecular condensates with data-driven mass-conserving reaction-diffusion systems 用数据驱动的质量守恒反应-扩散系统模拟生物分子凝聚物的相分离

IF 5.7 2区生物学

Structure Pub Date : 2025-06-25 DOI: 10.1016/j.str.2025.05.018

Cheng Li, Man-Ting Guo, Xiaoqing He, Quan-Xing Liu, Zhi Qi

引用次数: 0

Structural insights into the biotechnologically relevant reversible NADPH-oxidizing NiFe-hydrogenase from P. furiosus 从P. furiosus生物技术相关可逆nadph氧化nife -氢化酶的结构见解

IF 5.7 2区生物学

Structure Pub Date : 2025-06-25 DOI: 10.1016/j.str.2025.05.017

Xiansha Xiao, Gerrit J. Schut, Xiang Feng, Patrick M. McTernan, Dominik K. Haja, William N. Lanzilotta, Michael W.W. Adams, Huilin Li

引用次数: 0

Targeting ceramide synthases for the development of new antifungals 以神经酰胺合酶为靶点开发新型抗真菌药物

IF 5.7 2区生物学

Structure Pub Date : 2025-06-23 DOI: 10.1016/j.str.2025.05.016

Deveney Dasilva, Nivea Pereira de Sa, Kathryn Takemura, Kalani Jayanetti, Jeehyun Karen You, Nathalia Vieira de Sa, Gabriel Soares Matos, Andy Zhong, Can E. Senkal, Yusuf Hannun, Iwao Ojima, John Mallamo, John B. McCarthy, Maurizio Del Poeta

{"title":"Targeting ceramide synthases for the development of new antifungals","authors":"Deveney Dasilva, Nivea Pereira de Sa, Kathryn Takemura, Kalani Jayanetti, Jeehyun Karen You, Nathalia Vieira de Sa, Gabriel Soares Matos, Andy Zhong, Can E. Senkal, Yusuf Hannun, Iwao Ojima, John Mallamo, John B. McCarthy, Maurizio Del Poeta","doi":"10.1016/j.str.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.str.2025.05.016","url":null,"abstract":"Invasive fungal infections (IFIs) caused by pathogenic fungi are a major public health concern, particularly across various immunocompromised populations. Effective clinical management is currently hindered by limited treatment options. Fungal sphingolipids have emerged as potential antifungal targets based on cumulative evidence demonstrating that fungal sphingolipid metabolism is key to the virulence of pathogenic fungi. This study focuses on the sphingolipid metabolizing enzyme ceramide synthase. We developed an enzymatic assay to examine ceramide synthase activity and devised a high-throughput screening platform. Two synthetic compounds were identified that preferentially inhibit the fungal vs. the mammalian ceramide synthase activity. Further studies indicate that these compounds block fungal growth, with in silico and mutagenesis investigations revealing insights into the interactions between the inhibitors and the ceramide synthase active site. Together, our study establishes fungal ceramide synthase as a promising antifungal target and paves the way for new structure-activity relationship studies leveraging fungal sphingolipid metabolism.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"15 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Rapid hepatitis C virus replication machinery removal after antiviral treatment with DAA monitored by multimodal imaging 多模态成像监测的DAA抗病毒治疗后丙型肝炎病毒复制机制的快速清除

IF 5.7 2区生物学

Structure Pub Date : 2025-06-18 DOI: 10.1016/j.str.2025.05.015

Victoria Castro, Gema Calvo, Ana J. Pérez-Berná, Kevin Mamprin, Sergey Kapishnikov, David Rogers, Stephen O'Connor, Paul Sheridan, Kenneth Fahy, Eva Pereiro, Pablo Gastaminza

{"title":"Rapid hepatitis C virus replication machinery removal after antiviral treatment with DAA monitored by multimodal imaging","authors":"Victoria Castro, Gema Calvo, Ana J. Pérez-Berná, Kevin Mamprin, Sergey Kapishnikov, David Rogers, Stephen O'Connor, Paul Sheridan, Kenneth Fahy, Eva Pereiro, Pablo Gastaminza","doi":"10.1016/j.str.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.str.2025.05.015","url":null,"abstract":"Hepatitis C virus (HCV) replication causes a profound remodeling of the host endomembrane system. The availability of direct-acting antiviral (DAA) drugs provides an opportunity to define the ultrastructural events that follow viral replication blockade using confocal immunofluorescence, transmission electron microscopy (TEM) as well as correlative cryogenic light-soft X-ray tomography (CLSXT). Study of DAA-treated HCV replicons using CLSXT indicates that HCV-induced membranous alterations are no longer visible after 24 h of treatment and that a component of the replicase is located in pleomorphic, high-absorption contrast acidic organelles. TEM studies confirmed the rapid elimination of the viral machinery, and the concurrent appearance of large endo-lysosomes in DAA-treated cells. These and results by others suggest that HCV replication compartment may constantly be recycled by the endo-lysosomal system and that this equilibrium is unbalanced by DAA treatment, resulting in a transient activation of the endo-lysosomal system to achieve rapid viral machinery removal.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"12 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

High throughput cryo-EM provides structural understanding for modulators of the lysosomal ion channel TRPML1 高通量低温电镜为溶酶体离子通道TRPML1的调节剂提供了结构理解

IF 5.7 2区生物学

Structure Pub Date : 2025-06-17 DOI: 10.1016/j.str.2025.05.014

Judith Reeks, Pravin Mahajan, Mellissa Clark, Suzanna R. Cowan, Elena Di Daniel, Christopher P. Earl, Samantha Fisher, Rhian S. Holvey, Scott M. Jackson, Emyr Lloyd-Evans, Carmine M. Morgillo, Paul N. Mortenson, Marc O’Reilly, Caroline J. Richardson, Patrick Schöpf, Daniel M. Tams, Helen Waller-Evans, Simon E. Ward, Stuart Whibley, Pamela A. Williams, Christopher N. Johnson

{"title":"High throughput cryo-EM provides structural understanding for modulators of the lysosomal ion channel TRPML1","authors":"Judith Reeks, Pravin Mahajan, Mellissa Clark, Suzanna R. Cowan, Elena Di Daniel, Christopher P. Earl, Samantha Fisher, Rhian S. Holvey, Scott M. Jackson, Emyr Lloyd-Evans, Carmine M. Morgillo, Paul N. Mortenson, Marc O’Reilly, Caroline J. Richardson, Patrick Schöpf, Daniel M. Tams, Helen Waller-Evans, Simon E. Ward, Stuart Whibley, Pamela A. Williams, Christopher N. Johnson","doi":"10.1016/j.str.2025.05.014","DOIUrl":"https://doi.org/10.1016/j.str.2025.05.014","url":null,"abstract":"Access to high-resolution structural data for protein-ligand complexes is a prerequisite for structure-based medicinal chemistry, where the ability to iterate cycles of design-structure-redesign is highly desirable. For proteins refractory to X-ray crystallography, such as integral membrane proteins, enablement of high throughput structure determination by cryoelectron microscopy (cryo-EM) has the potential to be transformational for structure-based design. We have applied such an approach to the lysosomal ion channel transient receptor potential mucolipin 1 (TRPML1) in complex with ten chemically diverse modulators, both agonists and antagonists. The resulting depth of high-resolution structural data generated provides important insights into protein-ligand structure-function relationships, including mechanistic understanding of ligand-induced channel pore opening and closing. Moreover, the knowledge gained has the potential to support iterative design cycles toward improved modulators of this important biological target.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"11 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 continuous evolution of biomolecular force fields 生物分子力场的不断演化

IF 5.7 2区生物学

Structure Pub Date : 2025-06-16 DOI: 10.1016/j.str.2025.05.013

Xiaoli Lu, Jinfeng Chen, Jing Huang

引用次数: 0

A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain III类配体在内部和末端结合模式之间振荡，因为它与散乱PDZ结构域接合

IF 5.7 2区生物学

Structure Pub Date : 2025-06-13 DOI: 10.1016/j.str.2025.05.012

Jitender Kumar, Miroslav Micka, Jan Komárek, Tomáš Klumpler, Vojtěch Bystrý, Remco Sprangers, Cyril Bařinka, Vítězslav Bryja, Konstantinos Tripsianes

{"title":"A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain","authors":"Jitender Kumar, Miroslav Micka, Jan Komárek, Tomáš Klumpler, Vojtěch Bystrý, Remco Sprangers, Cyril Bařinka, Vítězslav Bryja, Konstantinos Tripsianes","doi":"10.1016/j.str.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.str.2025.05.012","url":null,"abstract":"One of the largest domain-motif interactomes in human involves PSD-95/Discs-large/ZO-1 (PDZ) domains. The framework for understanding the PDZ interactome is well established; however the functional dynamics associated with PDZ-ligand interactions are poorly understood. Here, we report a dual PDZ-binding mode that ascribes unique dynamic features to class III ligand recognition. The crystal structure revealed that the PDZ domain can recognize either of the carboxylate moieties (terminal or internal) present in the class III ligand and laid out the register rules responsible for the dual recognition. Variants of the ligand designed to retain one or the other carboxylate of the native sequence were sufficient for PDZ binding. The conformational dynamics of PDZ probed by NMR relaxation dispersion experiments demonstrated that the class III ligand is shuffling binding modes as it engages with the PDZ domain. Our mechanistic findings reveal yet another aspect of PDZ binding plasticity specific to class III ligands.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"26 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Redefining the role of the EryM acetyltransferase in natural product biosynthetic pathways 重新定义EryM乙酰转移酶在天然产物生物合成途径中的作用

IF 5.7 2区生物学

Structure Pub Date : 2025-06-13 DOI: 10.1016/j.str.2025.05.011

Yihua Li, Xunkun Liu, Natalia R. Harris, Jacquelyn R. Roberts, Estefanía Martínez Valdivia, Xinrui Ji, Janet L. Smith

{"title":"Redefining the role of the EryM acetyltransferase in natural product biosynthetic pathways","authors":"Yihua Li, Xunkun Liu, Natalia R. Harris, Jacquelyn R. Roberts, Estefanía Martínez Valdivia, Xinrui Ji, Janet L. Smith","doi":"10.1016/j.str.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.str.2025.05.011","url":null,"abstract":"The GNAT (GCN5-related N-acetyltransferase) superfamily comprises enzymes with a conserved fold and diverse catalytic activities, including primarily acyl transfer, with a few examples of decarboxylation. EryM, a GNAT from Saccharopolyspora erythraea, has been implicated in both erythromycin and erythrochelin biosynthesis, with dual functionality as an acetyltransferase and a decarboxylase. Despite an historical association with malonyl-coenzyme A decarboxylation activity, this dual activity has remained enigmatic as its close homologs were identified with only acyl transfer activity. Here, functional assays demonstrate that EryM catalyzes acyl transfer but lacks decarboxylation activity, challenging long-standing assumptions about its biosynthetic role. Crystal structures of EryM and an acetyl-CoA complex and comparison with homologs in siderophore pathways reveal a conserved catalytic pocket with an essential His and identically positioned side chains common to GNAT enzymes for N-acyl transfer from CoA to primary hydroxylamine substrates. Bioinformatic analysis defines a large GNAT subfamily broadly distributed in the microbial world.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"7 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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