Structure最新文献_第2页

Initial leads to combat streptogramin resistance generated from X-ray fragment screening against VatD 针对VatD的x射线片段筛选产生的链状gramin耐药性的初步结果

IF 5.7 2区生物学

Structure Pub Date : 2025-09-12 DOI: 10.1016/j.str.2025.08.017

Pooja Asthana, Sonya Lee, Christian M. MacDonald, Ian B. Seiple, James S. Fraser

{"title":"Initial leads to combat streptogramin resistance generated from X-ray fragment screening against VatD","authors":"Pooja Asthana, Sonya Lee, Christian M. MacDonald, Ian B. Seiple, James S. Fraser","doi":"10.1016/j.str.2025.08.017","DOIUrl":"https://doi.org/10.1016/j.str.2025.08.017","url":null,"abstract":"Streptogramins are potent antibiotics targeting bacterial ribosome. The synergistic binding of group A and B streptogramins to 50S-ribosome yields bactericidal effects. However, their efficacy is compromised by resistance mechanisms, including enzymatic acetylation of group A streptogramins by virginiamycin acetyltransferase (Vat) enzymes, which reduces their affinity for ribosomes. Using fragment-based drug discovery we identified starting points for development of VatD inhibitors. X-ray crystallography screening revealed three primary fragment-binding sites on VatD. In the acetyl-binding subsite, fragments stabilized distinct conformational states in critical residues, His82 and Trp121. In the antibiotic-binding site, two fragments formed interactions that could be leveraged for competitive inhibition. Elaborations of these fragments showed weak inhibition of VatD activity, indicating potential for further optimization. These findings establish initial hits that could restore streptogramin efficacy by targeting VatD directly, providing a structural foundation for inhibitor development against resistant bacterial strains.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"67 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043308","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

Structural analysis of ASCH domain-containing proteins and their implications for nucleotide processing 含ASCH结构域蛋白的结构分析及其对核苷酸加工的意义

IF 5.7 2区生物学

Structure Pub Date : 2025-09-11 DOI: 10.1016/j.str.2025.08.015

Chunyan Meng, Xiaoyan Shi, Wenting Guo, Xing Jian, Jie Zhao, Yan Wen, Ruiqi Wang, Yu Li, Sha Xu, Haitao Chen, Jiayu Zhang, Mingjia Chen, Hao Chen, Baixing Wu

{"title":"Structural analysis of ASCH domain-containing proteins and their implications for nucleotide processing","authors":"Chunyan Meng, Xiaoyan Shi, Wenting Guo, Xing Jian, Jie Zhao, Yan Wen, Ruiqi Wang, Yu Li, Sha Xu, Haitao Chen, Jiayu Zhang, Mingjia Chen, Hao Chen, Baixing Wu","doi":"10.1016/j.str.2025.08.015","DOIUrl":"https://doi.org/10.1016/j.str.2025.08.015","url":null,"abstract":"ASC-1 homology (ASCH) domain family proteins are believed to play essential roles in RNA metabolism, but detailed structural and functional information is limited. Research has shown that the E. coli enzyme YqfB, which contains an ASCH domain, has amidohydrolase activity, converting N4-acetylcytidine (ac4C) RNA nucleoside into cytidine. Here, we present the crystal structures of EcYqfB both in its unbound state and bound to a substrate. Our analysis reveals how the substrate interacts with the enzyme, offering insights into its catalytic mechanism. In vivo experiments further show that deleting EcYqfB does not change overall ac4C levels across various RNA types, indicating that EcYqfB specifically functions in ac4C nucleoside metabolism. We also determined the structures of two homologous proteins: mouse EOLA1 and the human TRIP4-ASCH domain, highlighting differences in their substrate preferences. These findings offer important insights for future research into the structure and function of the ASCH domain protein family.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"24 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043309","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

Genetically encoded FerriTag as a specific label for cryo-electron tomography 基因编码FerriTag作为冷冻电子断层扫描的特定标签

IF 5.7 2区生物学

Structure Pub Date : 2025-09-08 DOI: 10.1016/j.str.2025.08.013

Chang Wang, Amin Khosrozadeh, Ioan Iacovache, Benoît Zuber

引用次数: 0

Substrate and inhibitor binding of human GABA transporter 3 人GABA转运体的底物和抑制剂结合3

IF 5.7 2区生物学

Structure Pub Date : 2025-09-05 DOI: 10.1016/j.str.2025.08.012

Hao Xu, Yimin Zhang, Qinru Bai, Linli He, Qihao Chen, Yunlong Qiu, Renjie Li, Jie Yu, Jun Zhao, Yan Zhao

引用次数: 0

Structural insights into retinal-free microbial rhodopsins 无视网膜微生物视紫红质的结构见解

IF 5.7 2区生物学

Structure Pub Date : 2025-09-04 DOI: 10.1016/j.str.2025.08.005

Zhenmei Xu, Yuanzheng He

引用次数: 0

Wadjet—Keeping a watchful eye on circular DNA 瓦杰特——密切关注环状DNA

IF 5.7 2区生物学

Structure Pub Date : 2025-09-04 DOI: 10.1016/j.str.2025.08.006

Kevin D. Corbett, Amar Deep

引用次数: 0

Fungal kinesin-8 motors dimerize by folding their proximal tail domain into a compact helical bundle 真菌动力蛋白-8马达通过折叠其近端尾部结构域成紧凑的螺旋束进行二聚化

IF 5.7 2区生物学

Structure Pub Date : 2025-09-03 DOI: 10.1016/j.str.2025.08.011

Daria Trofimova, Caitlin Doubleday, Byron Hunter, Jesus Danilo Serrano Arevalo, Emma Davison, Eric Wen, Kim Munro, John S. Allingham

{"title":"Fungal kinesin-8 motors dimerize by folding their proximal tail domain into a compact helical bundle","authors":"Daria Trofimova, Caitlin Doubleday, Byron Hunter, Jesus Danilo Serrano Arevalo, Emma Davison, Eric Wen, Kim Munro, John S. Allingham","doi":"10.1016/j.str.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.str.2025.08.011","url":null,"abstract":"Kinesin-8 motors regulate kinetochore-microtubule dynamics and control spindle length and positioning. Certain isoforms achieve this by traversing microtubules, accumulating at plus-ends, and depolymerizing terminal αβ-tubulin subunits. While the kinesin-8 motor domain is well characterized, the tail domain regions are less understood. Using the Candida albicans Kip3 protein as a model for fungal kinesin-8, we present an X-ray crystal structure and hydrodynamic analysis of its motor-proximal tail segment, revealing its role in motor dimerization. This segment forms a compact, 92 Å-long four-helix bundle, rather than an elongated coiled-coil stalk seen in most kinesins. The bundle is stabilized primarily by interactions between helices one and three, with additional support from helices two and four. A flexible hinge bisects the bundle into two lobules, imparting mechanical pliability and asymmetric exterior surfaces. These unique features may facilitate interactions with regulatory elements or contribute to the functional versatility of kinesin-8 motors.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"11 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930865","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

Structural insights into outer membrane protein biogenesis in pathogenic Neisseria 致病性奈瑟菌外膜蛋白生物发生的结构见解

IF 5.7 2区生物学

Structure Pub Date : 2025-09-02 DOI: 10.1016/j.str.2025.08.009

Evan Billings, Zixing Fan, Moloud Aflaki Sooreshjani, James C. Gumbart, Nicholas Noinaj

{"title":"Structural insights into outer membrane protein biogenesis in pathogenic Neisseria","authors":"Evan Billings, Zixing Fan, Moloud Aflaki Sooreshjani, James C. Gumbart, Nicholas Noinaj","doi":"10.1016/j.str.2025.08.009","DOIUrl":"https://doi.org/10.1016/j.str.2025.08.009","url":null,"abstract":"N. gonorrhoeae (Ngo) causes the sexually transmitted infection gonorrhea with ∼106 million infections worldwide annually. Ngo infections can result in an increased risk of acquiring HIV, infertility, and blindness. To combat Ngo infections, we report the cryoelectron microscopy (cryo-EM) structure of the Ngo β-barrel assembly machinery (NgBAM), which is responsible for the biogenesis of β-barrel outer membrane proteins (OMPs). NgBAM was observed in an inward-open state; however, the polypeptide transport-associated (POTRA) domains more closely match those found in the outward-open state in E. coli β-barrel assembly machinery (BAM). The barrel seam of NgBamA consists of partial pairing of strand β1 with β16; no outward-open state of NgBAM was observed. Molecular dynamics (MD) simulations reveal unique overall dynamics and interplay between the POTRA domains of NgBamA and NgBamD. We propose that in Ngo, initial recognition occurs in the inward-open state where the last strand of the OMP partially pairs with β1 of NgBamA and must compete off β16.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"14 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928517","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

Characterization of the OMP biogenesis machinery in Fusobacterium nucleatum 核梭杆菌OMP生物发生机制的表征

IF 5.7 2区生物学

Structure Pub Date : 2025-09-01 DOI: 10.1016/j.str.2025.08.008

Claire Overly Cottom, Eva Heinz, Satchal Erramilli, Anthony Kossiakoff, Daniel J. Slade, Nicholas Noinaj

引用次数: 0

Code to complex: AI-driven de novo binder design 代码复杂：人工智能驱动的从头设计

IF 5.7 2区生物学

Structure Pub Date : 2025-09-01 DOI: 10.1016/j.str.2025.08.007

Daniel R. Fox, Cyntia Taveneau, Janik Clement, Rhys Grinter, Gavin J. Knott

引用次数: 0