Acta crystallographica. Section F, Structural biology communications最新文献_第6页

Structural characterization of dUTPase from Legionella pneumophila 嗜肺军团菌dutp酶的结构特征。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-17 DOI: 10.1107/S2053230X25001815

Chi L. Nguyen, Abigail R. Tramell, Jordan O. Norman, Jan Abendroth, Kayleigh F. Barrett, Justin K. Craig, Thomas E. Edwards, Donald D. Lorimer, Wesley C. Van Voorhis, Krystle J. McLaughlin

{"title":"Structural characterization of dUTPase from Legionella pneumophila","authors":"Chi L. Nguyen, Abigail R. Tramell, Jordan O. Norman, Jan Abendroth, Kayleigh F. Barrett, Justin K. Craig, Thomas E. Edwards, Donald D. Lorimer, Wesley C. Van Voorhis, Krystle J. McLaughlin","doi":"10.1107/S2053230X25001815","DOIUrl":"10.1107/S2053230X25001815","url":null,"abstract":"Cellular deoxyuridine 5′-triphosphate nucleotidohydrolases (dUTPases) catalyze the hydrolysis of deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP) and pyrophosphate (PPi). dUTPase is an essential metabolic enzyme which maintains the homeostatic dTTP:dUTP ratio. As DNA polymerases are unable to distinguish between thymine and uracil during replication, the dTTP:dUTP ratio is essential for preventing the misincorporation of uracil into DNA. In the absence of dUTPase regulation of the dTTP:dUTP ratio, many DNA double-strand breaks are induced by DNA-repair enzymes, which may ultimately lead to cell death. Legionnaires' disease is a rare but severe respiratory infection caused primarily by Legionella pneumophila serogroup 1. Increased characterization of the L. pneumophila proteome is of interest for the development of new treatments. Many DNA metabolism proteins have yet to be characterized in L. pneumophila, including dUTPase. Here, we present analysis of two crystal structures of L. pneumophila dUTPase in its apo and dUMP-bound states, determined to 1.80 and 1.95 Å resolution, respectively. The structures were solved by the Seattle Structural Genomics Center for Infectious Disease (SSGCID) as part of their mission to determine structures of proteins and other molecules with an important biological role in human pathogens.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":"81 4","pages":"155-162"},"PeriodicalIF":1.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646647","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 S-adenosylmethionine-dependent mycolic acid synthase UmaA from Mycobacterium tuberculosis 结核分枝杆菌s -腺苷甲硫氨酸依赖霉菌酸合成酶UmaA的晶体结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-10 DOI: 10.1107/S2053230X25001530

Sean Teng, Jie Wang, Collin D. Sroge, Jan Abendroth, Donald D. Lorimer, Peter S. Horanyi, Thomas E. Edwards, Logan Tillery, Justin K. Craig, Wesley C. Van Voorhis, Peter J. Myler, Craig L. Smith

{"title":"Crystal structure of the S-adenosylmethionine-dependent mycolic acid synthase UmaA from Mycobacterium tuberculosis","authors":"Sean Teng, Jie Wang, Collin D. Sroge, Jan Abendroth, Donald D. Lorimer, Peter S. Horanyi, Thomas E. Edwards, Logan Tillery, Justin K. Craig, Wesley C. Van Voorhis, Peter J. Myler, Craig L. Smith","doi":"10.1107/S2053230X25001530","DOIUrl":"10.1107/S2053230X25001530","url":null,"abstract":"Mycobacterium tuberculosis is a Gram-positive bacillus that causes tuberculosis and is a leading cause of mortality worldwide. This disease is a growing health threat due to the occurrence of multidrug resistance. Mycolic acids are essential for generating cell walls and their modification is important to the virulence and persistence of M. tuberculosis. A family of S-adenosylmethionine-dependent mycolic acid synthases modify mycolic acids and represent promising drug targets. UmaA is currently the least-understood member of this family. This paper describes the crystal structure of UmaA. UmaA is a monomer composed of two domains: a structurally conserved SAM-binding domain and a variable substrate-binding auxiliary domain. Fortuitously, our structure contains a nitrate in the active site, a structural mimic of carbonate, which is a known general base in cyclopropane-adding synthases. Further investigation indicated that the structure of the N-terminus is highly flexible. Finally, we have identified S-adenosyl-N-decyl-aminoethyl as a promising potential inhibitor.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":"81 4","pages":"146-154"},"PeriodicalIF":1.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584263","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

Analysis of Burkholderia pseudomallei IspF in complex with sulfapyridine, sulfamonomethoxine, ethoxzolamide and acetazolamide 伪马氏伯克氏菌IspF与磺胺吡啶、磺胺甲氧胺、乙氧唑胺、乙酰唑胺配合物的分析。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-04 DOI: 10.1107/S2053230X25001414

Dakota Grote, Christopher G. Stewart, Drashti G. Daraji, Parisa Enayati, Kristina N. Braverman, CeAnn Romanaggi, Madison J. Bolejack, Jason K. Yano, Jan Abendroth, David M. Dranow, Phillip G. Pierce, Donald D. Lorimer, Peter S. Horanyi, Bart L. Staker, Thomas E. Edwards, Peter J. Myler, James R. Horn, Timothy J. Hagen

{"title":"Analysis of Burkholderia pseudomallei IspF in complex with sulfapyridine, sulfamonomethoxine, ethoxzolamide and acetazolamide","authors":"Dakota Grote, Christopher G. Stewart, Drashti G. Daraji, Parisa Enayati, Kristina N. Braverman, CeAnn Romanaggi, Madison J. Bolejack, Jason K. Yano, Jan Abendroth, David M. Dranow, Phillip G. Pierce, Donald D. Lorimer, Peter S. Horanyi, Bart L. Staker, Thomas E. Edwards, Peter J. Myler, James R. Horn, Timothy J. Hagen","doi":"10.1107/S2053230X25001414","DOIUrl":"10.1107/S2053230X25001414","url":null,"abstract":"The methylerythritol phosphate (MEP) pathway is a metabolic pathway that produces the isoprenoids isopentyl pyrophosphate and dimethylallyl pyrophosphate. Notably, the MEP pathway is present in bacteria and not in mammals, which makes the enzymes of the MEP pathway attractive targets for the discovery of new anti-infective agents due to the reduced chances of off-target interactions leading to side effects. There are seven enzymes in the MEP pathway, the fifth of which is IspF. Crystal structures of Burkholderia pseudomallei IspF were determined with five different sulfonamide ligands bound. The sulfonamide-containing ligands were ethoxzolamide, acetazolamide, sulfapyridine and sulfamonomethoxine. The fifth bound ligand was a synthetic analog of acetazolamide. All ligands coordinated to the active-site Zn+2 ion through the sulfonamide group, although sulfapyridine and sulfamonomethoxine, both of which are known antibacterial agents, possess similar binding interactions that are distinct from the other three sulfonamides. These structural data will aid in the discovery of new IspF inhibitors.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":"81 4","pages":"138-145"},"PeriodicalIF":1.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539693","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}

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The crystal structures of apo and tryptophan-bound tryptophanyl-tRNA synthetase from Neisseria gonorrhoeae 淋病奈瑟菌载子和色氨酸结合色氨酸- trna合成酶的晶体结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-04 DOI: 10.1107/S2053230X25001311

Jessika Baral, David Song, Thomas E. Edwards, David M. Dranow, Donald D. Lorimer, Bart L. Staker, Peter Myler, Craig L. Smith

{"title":"The crystal structures of apo and tryptophan-bound tryptophanyl-tRNA synthetase from Neisseria gonorrhoeae","authors":"Jessika Baral, David Song, Thomas E. Edwards, David M. Dranow, Donald D. Lorimer, Bart L. Staker, Peter Myler, Craig L. Smith","doi":"10.1107/S2053230X25001311","DOIUrl":"10.1107/S2053230X25001311","url":null,"abstract":"Neisseria gonorrhoeae, the causative agent of the human disease gonorrhea, is the second most common sexually transmitted pathogen in the United States. Gonorrhea has a significantly high morbidity rate due to the ability of N. gonorrhoeae to rapidly develop antibiotic resistance. In this paper, crystal structures of tryptophanyl-tRNA synthetase (TrpRS) from N. gonorrhoeae (NgTrpRS) were determined in both its apo form and in complex with tryptophan. The structures reveal conserved HIGH and KMSKS motifs critical for ATP binding and catalysis, and highlight conformational changes in the active site upon tryptophan binding, including a methionine flip and the rearrangement of hydrogen-bonding residues. Structural alignments with human TrpRS isoforms demonstrate significant differences between the bacterial and human cytosolic forms, particularly in their active sites. While NgTrpRS and human mitochondrial TrpRS share conserved catalytic residues that are essential for binding tryptophan and indolmycin, the cytosolic TrpRS contains substitutions that introduce steric hindrance, limiting the binding of indolmycin. These results provide insight for the development of inhibitors targeting bacterial TrpRS without affecting the human mitochondrial or cytosolic isoforms, contributing to efforts to combat antibiotic-resistant N. gonorrhoeae infections.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":"81 4","pages":"130-137"},"PeriodicalIF":1.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536335","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 : 2025-03-04

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The first report of structural analysis of a nucleic acid using crystals grown in space. 利用在太空中生长的晶体对核酸进行结构分析的第一份报告。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.1107/S2053230X25000810

Shin Ando, Moena Takahashi, Jiro Kondo

{"title":"The first report of structural analysis of a nucleic acid using crystals grown in space.","authors":"Shin Ando, Moena Takahashi, Jiro Kondo","doi":"10.1107/S2053230X25000810","DOIUrl":"10.1107/S2053230X25000810","url":null,"abstract":"For the success of structure-based drug design, three-dimensional structures solved by X-ray crystallography at atomic resolution are mandatory. In order to obtain high-quality single crystals with strong diffraction power, crystallization under microgravity conditions has been attempted for proteins. Since nucleic acid duplexes have chemical, structural and crystallographic characteristics that differ from those of globular proteins, such as intermolecular repulsion due to negative charge and molecular and crystallographic anisotropies, it is interesting to investigate whether microgravity crystallization improves the crystal growth of nucleic acids. However, to our knowledge there has been only one report on nucleic acid crystallization in a microgravity environment, and there have been no reports of successful structural analysis. Here, we conducted the crystallization of a DNA/RNA heteroduplex in space. The heteroduplex was successfully crystallized in a microgravity environment, and the size and appearance of the crystals were improved compared with control experiments conducted on Earth. Although the effect of the counter-diffusion method is likely to be more significant than the effect of microgravity in this study, we were able to analyze the structure at a higher resolution (1.4 Å) than our previously reported crystal structure (1.9 Å).","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":" ","pages":"95-100"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397667","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

A two-in-one expression construct for biophysical and structural studies of the human pregnane X receptor ligand-binding domain, a pharmaceutical and environmental target. 一个二合一表达构建体，用于人类妊娠X受体配体结合域的生物物理和结构研究，一个药物和环境靶标。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-01 Epub Date: 2025-02-09 DOI: 10.1107/S2053230X2500069X

Coralie Carivenc, Guillaume Laconde, Pauline Blanc, Muriel Amblard, William Bourguet, Vanessa Delfosse

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Cryo-EM structures of apo and atorvastatin-bound human 3-hydroxy-3-methylglutaryl-coenzyme A reductase. 载脂蛋白和阿托伐他汀结合的人3-羟基-3-甲基戊二酰辅酶A还原酶的低温电镜结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-01 Epub Date: 2025-02-20 DOI: 10.1107/S2053230X25001098

Manikandan Karuppasamy, Jason van Rooyen

{"title":"Cryo-EM structures of apo and atorvastatin-bound human 3-hydroxy-3-methylglutaryl-coenzyme A reductase.","authors":"Manikandan Karuppasamy, Jason van Rooyen","doi":"10.1107/S2053230X25001098","DOIUrl":"10.1107/S2053230X25001098","url":null,"abstract":"The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) regulates the level of cholesterol by catalysing the formation/production of mevalonate and has therefore become an important pharmaceutical target for coronary heart disease. Here, we report the cryo-EM structure of the catalytic part of the enzyme in the apo form and bound with its inhibitor atorvastatin, a commonly used drug in cardiovascular disease, at resolutions of 2.1 and 2.3 Å, respectively. In the cryo-EM maps, part of the N-domain corresponding to amino acids 439-487 is well ordered and could be modelled completely. Atorvastatin molecules were found to occupy all four active sites of the tetrameric complex, and the binding does not alter the conformation of the protein or the active site. The method described here exploits graphene oxide as an additional support and could be used as an alternative to elucidate the structures of pharmaceutical target compounds that are difficult to co-crystallize with human HMGR and for sparsely available samples in drug discovery.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":" ","pages":"118-122"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456586","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

Redox-dependent hydrogen-bond network rearrangement of ferredoxin-NADP⁺ reductase revealed by high-resolution X-ray and neutron crystallography. 高分辨率x射线和中子晶体学揭示的铁氧化还原蛋白- nadp +还原酶的氧化还原依赖氢键网络重排。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-01 Epub Date: 2025-02-06 DOI: 10.1107/S2053230X25000524

Midori Uenaka, Yusuke Ohnishi, Akane Ise, Jiang Yu, Naomine Yano, Katsuhiro Kusaka, Hideaki Tanaka, Genji Kurisu

{"title":"Redox-dependent hydrogen-bond network rearrangement of ferredoxin-NADP+ reductase revealed by high-resolution X-ray and neutron crystallography.","authors":"Midori Uenaka, Yusuke Ohnishi, Akane Ise, Jiang Yu, Naomine Yano, Katsuhiro Kusaka, Hideaki Tanaka, Genji Kurisu","doi":"10.1107/S2053230X25000524","DOIUrl":"10.1107/S2053230X25000524","url":null,"abstract":"High-resolution X-ray and neutron crystallography were employed to elucidate redox-dependent structural changes in ferredoxin-NADP+ reductase (FNR) from maize. This study focused on the rearrangement of hydrogen-bond networks upon FAD reduction. The X-ray structures of wild-type FNR in oxidized and reduced states were refined to 1.15 and 1.10 Å resolution, respectively, revealing no large structural changes in the main-chain backbones. Neutron crystallography provided complementary insights, confirming protonation at N1 and N5 of the isoalloxazine ring and visualizing hydrogen bonds that were undetectable by X-ray analysis. These findings illuminate the dynamic reorganization of water-mediated hydrogen-bond networks during redox transitions, which may underpin the redox-dependent modulation of partner binding by FNR. This integrated structural approach highlights the synergistic use of X-ray and neutron crystallography in studying redox-active proteins.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":" ","pages":"73-84"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363186","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}

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LOPAC library screening identifies suramin as a TRIM21 binder with a unique binding mode revealed by crystal structure. LOPAC文库筛选鉴定苏拉明是一种TRIM21结合剂，其晶体结构显示出独特的结合模式。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-03-01 Epub Date: 2025-02-16 DOI: 10.1107/S2053230X25000913

Yeojin Kim, Stefan Knapp, Andreas Krämer

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