Acta crystallographica. Section F, Structural biology communications最新文献

Structures of Brucella ovis leucine-, isoleucine-, valine-, threonine- and alanine-binding protein reveal a conformationally flexible peptide-binding cavity. 布鲁氏菌亮氨酸、异亮氨酸、缬氨酸、苏氨酸和丙氨酸结合蛋白的结构揭示了一个构象灵活的肽结合腔。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-09-01 Epub Date: 2024-08-23 DOI: 10.1107/S2053230X24007027

Graham Chakafana, Reghan Boswell, Andrew Chandler, Krishelle A Jackson, Sanai Neblett, Tyler Postal, Sandhya Subramanian, Jan Abendroth, Peter J Myler, Oluwatoyin A Asojo

{"title":"Structures of Brucella ovis leucine-, isoleucine-, valine-, threonine- and alanine-binding protein reveal a conformationally flexible peptide-binding cavity.","authors":"Graham Chakafana, Reghan Boswell, Andrew Chandler, Krishelle A Jackson, Sanai Neblett, Tyler Postal, Sandhya Subramanian, Jan Abendroth, Peter J Myler, Oluwatoyin A Asojo","doi":"10.1107/S2053230X24007027","DOIUrl":"10.1107/S2053230X24007027","url":null,"abstract":"Brucella ovis is an etiologic agent of ovine epididymitis and brucellosis that causes global devastation in sheep, rams, goats, small ruminants and deer. There are no cost-effective methods for the worldwide eradication of ovine brucellosis. B. ovis and other protein targets from various Brucella species are currently in the pipeline for high-throughput structural analysis at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), with the aim of identifying new therapeutic targets. Furthermore, the wealth of structures generated are effective tools for teaching scientific communication, structural science and biochemistry. One of these structures, B. ovis leucine-, isoleucine-, valine-, threonine- and alanine-binding protein (BoLBP), is a putative periplasmic amino acid-binding protein. BoLBP shares less than 29% sequence identity with any other structure in the Protein Data Bank. The production, crystallization and high-resolution structures of BoLBP are reported. BoLBP is a prototypical bacterial periplasmic amino acid-binding protein with the characteristic Venus flytrap topology of two globular domains encapsulating a large central cavity containing the peptide-binding region. The central cavity contains small molecules usurped from the crystallization milieu. The reported structures reveal the conformational flexibility of the central cavity in the absence of bound peptides. The structural similarity to other LBPs can be exploited to accelerate drug repurposing.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034915","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

Crystallographic fragment screen of the c-di-AMP-synthesizing enzyme CdaA from Bacillus subtilis. 枯草芽孢杆菌 c-di-AMP 合成酶 CdaA 的晶体片段筛选。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-09-01 Epub Date: 2024-08-23 DOI: 10.1107/S2053230X24007039

Tim Garbers, Piotr Neumann, Jan Wollenhaupt, Achim Dickmanns, Manfred S Weiss, Ralf Ficner

{"title":"Crystallographic fragment screen of the c-di-AMP-synthesizing enzyme CdaA from Bacillus subtilis.","authors":"Tim Garbers, Piotr Neumann, Jan Wollenhaupt, Achim Dickmanns, Manfred S Weiss, Ralf Ficner","doi":"10.1107/S2053230X24007039","DOIUrl":"10.1107/S2053230X24007039","url":null,"abstract":"Crystallographic fragment screening has become a pivotal technique in structure-based drug design, particularly for bacterial targets with a crucial role in infectious disease mechanisms. The enzyme CdaA, which synthesizes an essential second messenger cyclic di-AMP (c-di-AMP) in many pathogenic bacteria, has emerged as a promising candidate for the development of novel antibiotics. To identify crystals suitable for fragment screening, CdaA enzymes from Streptococcus pneumoniae, Bacillus subtilis and Enterococcus faecium were purified and crystallized. Crystals of B. subtilis CdaA, which diffracted to the highest resolution of 1.1 Å, were used to perform the screening of 96 fragments, yielding data sets with resolutions spanning from 1.08 to 1.87 Å. A total of 24 structural hits across eight different sites were identified. Four fragments bind to regions that are highly conserved among pathogenic bacteria, specifically the active site (three fragments) and the dimerization interface (one fragment). The coordinates of the three active-site fragments were used to perform an in silico drug-repurposing screen using the OpenEye suite and the DrugBank database. This screen identified tenofovir, an approved drug, that is predicted to interact with the ATP-binding region of CdaA. Its inhibitory potential against pathogenic E. faecium CdaA has been confirmed by ITC measurements. These findings not only demonstrate the feasibility of this approach for identifying lead compounds for the design of novel antibacterial agents, but also pave the way for further fragment-based lead-optimization efforts targeting CdaA.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034913","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

Crystal structure of the Rib domain of the cell-wall-anchored surface protein from Limosilactobacillus reuteri 雷特氏乳杆菌细胞壁锚定表面蛋白 Rib 结构域的晶体结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-28 DOI: 10.1107/S2053230X24007970

Yi Xue, Zhen Wu, Xue Kang

{"title":"Crystal structure of the Rib domain of the cell-wall-anchored surface protein from Limosilactobacillus reuteri","authors":"Yi Xue, Zhen Wu, Xue Kang","doi":"10.1107/S2053230X24007970","DOIUrl":"10.1107/S2053230X24007970","url":null,"abstract":"The immunoglobulin (Ig)-like domain is found in a broad range of proteins with diverse functional roles. While an essential β-sandwich fold is maintained, considerable structural variations exist and are critical for functional diversity. The Rib-domain family, primarily found as tandem-repeat modules in the surface proteins of Gram-positive bacteria, represents another significant structural variant of the Ig-like fold. However, limited structural and functional exploration of this family has been conducted, which significantly restricts the understanding of its evolution and significance within the Ig superclass. In this work, a high-resolution crystal structure of a Rib domain derived from the probiotic bacterium Limosilactobacillus reuteri is presented. This protein, while sharing significant structural similarity with homologous domains from other bacteria, exhibits a significantly increased thermal resistance. The potential structural features contributing to this stability are discussed. Moreover, the presence of two copper-binding sites, with one positioned on the interface, suggests potential functional roles that warrant further investigation.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085851","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

Crystal structure of the GDP-bound human M-RAS protein in two crystal forms 两种晶体形态的 GDP 结合型人类 M-RAS 蛋白的晶体结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-28 DOI: 10.1107/S2053230X24007969

Stephanie M. Bester, Rebecca Abrahamsen, Luiza Rodrigues Samora, Wen-I Wu, Tung-Chung Mou

引用次数: 0

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-23

引用次数: 0

Enhancing the apo protein tyrosine phosphatase non-receptor type 2 crystal soaking strategy through inhibitor-accessible binding sites 通过抑制剂可进入的结合位点增强 apo 蛋白酪氨酸磷酸酶非受体 2 型晶体浸泡策略。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-23 DOI: 10.1107/S2053230X24007866

Stephanie M. Bester, Rebecca Linwood, Ryoko Kataoka, Wen-I Wu, Tung-Chung Mou

{"title":"Enhancing the apo protein tyrosine phosphatase non-receptor type 2 crystal soaking strategy through inhibitor-accessible binding sites","authors":"Stephanie M. Bester, Rebecca Linwood, Ryoko Kataoka, Wen-I Wu, Tung-Chung Mou","doi":"10.1107/S2053230X24007866","DOIUrl":"10.1107/S2053230X24007866","url":null,"abstract":"Protein tyrosine phosphatase non-receptor type 2 (PTPN2) has recently been recognized as a promising target for cancer immunotherapy. Despite extensive structural and functional studies of other protein tyrosine phosphatases, there is limited structural understanding of PTPN2. Currently, there are only five published PTPN2 structures and none are truly unbound due to the presence of a mutation, an inhibitor or a loop (related to crystal packing) in the active site. In this report, a novel crystal packing is revealed that resulted in a true apo PTPN2 crystal structure with an unbound active site, allowing the active site to be observed in a native apo state for the first time. Key residues related to accommodation in the active site became identifiable upon comparison with previously published PTPN2 structures. Structures of PTPN2 in complex with an established PTPN1 active-site inhibitor and an allosteric inhibitor were achieved through soaking experiments using these apo PTPN2 crystals. The increased structural understanding of apo PTPN2 and the ability to soak in inhibitors will aid the development of future PTPN2 inhibitors.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034914","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

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-23

引用次数: 0

Richard Alexander Pauptit 1954–2024 理查德-亚历山大-保普特 1954-2024

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-05 DOI: 10.1107/S2053230X24007064

Caitriona Dennis, Dean Derbyshire, Joacim Jaeger, Alan Riboldi-Tunnicliffe

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Tricks and tips for trips 旅行的技巧和提示。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-05 DOI: 10.1107/S2053230X24007593

Mark J. van Raaij

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Preparing research samples for safe arrival at centers and facilities: recipes for successful experiments. 为研究样本安全抵达中心和设施做好准备：成功实验的秘诀。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2024-08-01 Epub Date: 2024-07-11 DOI: 10.1107/S2053230X24006174

Sarah E J Bowman, James Byrnes, Silvia Russi, Christina M Zimanyi

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