Journal of structural and functional genomics最新文献_第3页

Solution NMR structures of homeodomains from human proteins ALX4, ZHX1, and CASP8AP2 contribute to the structural coverage of the Human Cancer Protein Interaction Network. 人类蛋白ALX4、ZHX1和CASP8AP2同源结构域的溶液核磁共振结构有助于人类癌症蛋白相互作用网络的结构覆盖。

Journal of structural and functional genomics Pub Date : 2014-12-01 Epub Date: 2014-06-19 DOI: 10.1007/s10969-014-9184-z

Xianzhong Xu, Surya V S R K Pulavarti, Alexander Eletsky, Yuanpeng Janet Huang, Thomas B Acton, Rong Xiao, John K Everett, Gaetano T Montelione, Thomas Szyperski

引用次数: 1

Structural and functional analysis of the anti-malarial drug target prolyl-tRNA synthetase. 抗疟疾药物靶点脯氨酸- trna合成酶的结构与功能分析。

Journal of structural and functional genomics Pub Date : 2014-12-01 Epub Date: 2014-07-22 DOI: 10.1007/s10969-014-9186-x

Vitul Jain, Haruhisa Kikuchi, Yoshiteru Oshima, Amit Sharma, Manickam Yogavel

{"title":"Structural and functional analysis of the anti-malarial drug target prolyl-tRNA synthetase.","authors":"Vitul Jain, Haruhisa Kikuchi, Yoshiteru Oshima, Amit Sharma, Manickam Yogavel","doi":"10.1007/s10969-014-9186-x","DOIUrl":"https://doi.org/10.1007/s10969-014-9186-x","url":null,"abstract":"Aminoacyl-tRNA synthetases (aaRSs) drive protein translation in cells and hence these are essential enzymes across life. Inhibition of these enzymes can halt growth of an organism by stalling protein translation. Therefore, small molecule targeting of aaRS active sites is an attractive avenue from the perspective of developing anti-infectives. Febrifugine and its derivatives like halofuginone (HF) are known to inhibit prolyl-tRNA synthetase of malaria parasite Plasmodium falciparum. Here, we present functional and crystallographic data on P. falciparum prolyl-tRNA synthetase (PfPRS). Using immunofluorescence data, we show that PfPRS is exclusively resident in the parasite cytoplasm within asexual blood stage parasites. The inhibitor HF interacts strongly with PfPRS in a non-competitive binding mode in presence or absence of ATP analog. Intriguingly, the two monomers that constitute dimeric PfPRS display significantly different conformations in their active site regions. The structural analyses presented here provide a framework for development of febrifugine derivatives that can seed development of new anti-malarials. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":"15 4","pages":"181-90"},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9186-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32522441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 36

Development of a hexahistidine-3× FLAG-tandem affinity purification method for endogenous protein complexes in Pichia pastoris. 在 Pichia pastoris 中开发内源蛋白复合物的六脒-3×FLAG-串联亲和纯化方法。

Journal of structural and functional genomics Pub Date : 2014-12-01 Epub Date: 2014-11-15 DOI: 10.1007/s10969-014-9190-1

Toshiaki Higo, Noriyuki Suka, Haruhiko Ehara, Masatoshi Wakamori, Shin Sato, Hideaki Maeda, Shun-ichi Sekine, Takashi Umehara, Shigeyuki Yokoyama

引用次数: 0

Solution NMR structures of immunoglobulin-like domains 7 and 12 from obscurin-like protein 1 contribute to the structural coverage of the Human Cancer Protein Interaction Network. 免疫球蛋白样结构域7和12的溶液核磁共振结构有助于人类癌症蛋白相互作用网络的结构覆盖。

Journal of structural and functional genomics Pub Date : 2014-12-01 Epub Date: 2014-07-03 DOI: 10.1007/s10969-014-9185-y

Surya V S R K Pulavarti, Yuanpeng J Huang, Kari Pederson, Thomas B Acton, Rong Xiao, John K Everett, James H Prestegard, Gaetano T Montelione, Thomas Szyperski

引用次数: 0

Structural characterization of the putative ABC-type 2 transporter from Thermotoga maritima MSB8. 推测产自海洋热菌MSB8的abc - 2型转运体的结构表征。

Journal of structural and functional genomics Pub Date : 2014-12-01 Epub Date: 2014-10-12 DOI: 10.1007/s10969-014-9189-7

Ekaterina V Filippova, Karolina L Tkaczuk, Maksymilian Chruszcz, Xiaohui Xu, Alexei Savchenko, Aled Edwards, Wladek Minor

引用次数: 1

Substrate selectivity of bacterial monoacylglycerol lipase based on crystal structure. 基于晶体结构的细菌单酰基甘油脂肪酶的底物选择性。

Journal of structural and functional genomics Pub Date : 2014-09-01 Epub Date: 2014-06-04 DOI: 10.1007/s10969-014-9181-2

Toshiharu Tsurumura, Hideaki Tsuge

{"title":"Substrate selectivity of bacterial monoacylglycerol lipase based on crystal structure.","authors":"Toshiharu Tsurumura, Hideaki Tsuge","doi":"10.1007/s10969-014-9181-2","DOIUrl":"https://doi.org/10.1007/s10969-014-9181-2","url":null,"abstract":"Lipases, which are conserved from bacteria to mammals, catalyze the hydrolysis of acylglycerol to free fatty acids and glycerol. Monoacylglycerol lipase (MGL) specifically catalyzes the hydrolysis of monoacylglycerol. Although there have been numerous studies of the structure of lipases, there have been few studies of MGL. Here, we report the crystal structure of authentic MGL isolated from Bacillus sp. H257 (bMGL). The crystal diffracts to 1.96 Å resolution. It belongs to space group P21212, and the unit cell parameters are a=99.7 Å, b=106.1 Å and c=43.0 Å. As in other lipases, three structural features for lipase activity are conserved in bMGL: the glycine-X-serine-X-glycine motif, catalytic triad and cap region. The structure of bMGL appears to be closed, as the cap region covers the active site entrance. The isolated bMGL hydrolyzed 2-AG, a known human MGL-specific substrate. Based on a 2-AG bound model, we discuss the substrate selectivity. The functional and structural features of bMGL provide insight how its substrate selectivity is determined and how specific inhibitors of bacterial MGL could be designed, which may be useful for development of novel antibiotics.","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":" ","pages":"83-9"},"PeriodicalIF":0.0,"publicationDate":"2014-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9181-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32394513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Crystal structure of the eukaryotic translation initiation factor 2A from Schizosaccharomyces pombe. 裂糖酵母翻译起始因子2A的晶体结构。

Journal of structural and functional genomics Pub Date : 2014-09-01 Epub Date: 2014-02-26 DOI: 10.1007/s10969-014-9177-y

Kazuhiro Kashiwagi, Takuhiro Ito, Shigeyuki Yokoyama

引用次数: 7

Structural genomics studies of human caries pathogen Streptococcus mutans. 人类龋齿致病菌变形链球菌的结构基因组学研究。

Journal of structural and functional genomics Pub Date : 2014-09-01 Epub Date: 2014-01-29 DOI: 10.1007/s10969-014-9172-3

Lanfen Li, Jie Nan, Dan Li, Erik Brostromer, Zixi Wang, Cong Liu, Qiaoming Hou, Xuexin Fan, Zhaoyang Ye, Xiao-Dong Su

{"title":"Structural genomics studies of human caries pathogen Streptococcus mutans.","authors":"Lanfen Li, Jie Nan, Dan Li, Erik Brostromer, Zixi Wang, Cong Liu, Qiaoming Hou, Xuexin Fan, Zhaoyang Ye, Xiao-Dong Su","doi":"10.1007/s10969-014-9172-3","DOIUrl":"https://doi.org/10.1007/s10969-014-9172-3","url":null,"abstract":"Gram-positive bacterium Streptococcus mutans is the primary causative agent of human dental caries. To better understand this pathogen at the atomic structure level and to establish potential drug and vaccine targets, we have carried out structural genomics research since 2005. To achieve the goal, we have developed various in-house automation systems including novel high-throughput crystallization equipment and methods, based on which a large-scale, high-efficiency and low-cost platform has been establish in our laboratory. From a total of 1,963 annotated open reading frames, 1,391 non-membrane targets were selected prioritized by protein sequence similarities to unknown structures, and clustered by restriction sites to allow for cost-effective high-throughput conventional cloning. Selected proteins were over-expressed in different strains of Escherichia coli. Clones expressed soluble proteins were selected, expanded, and expressed proteins were purified and subjected to crystallization trials. Finally, protein crystals were subjected to X-ray analysis and structures were determined by crystallographic methods. Using the previously established procedures, we have so far obtained more than 200 kinds of protein crystals and 100 kinds of crystal structures involved in different biological pathways. In this paper we demonstrate and review a possibility of performing structural genomics studies at moderate laboratory scale. Furthermore, the techniques and methods developed in our study can be widely applied to conventional structural biology research practice. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":" ","pages":"91-9"},"PeriodicalIF":0.0,"publicationDate":"2014-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9172-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32070202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Crystal structures of the S6K1 kinase domain in complexes with inhibitors. 抑制剂配合物中S6K1激酶结构域的晶体结构。

Journal of structural and functional genomics Pub Date : 2014-09-01 Epub Date: 2014-07-31 DOI: 10.1007/s10969-014-9188-8

Hideaki Niwa, Junko Mikuni, Shunta Sasaki, Yuri Tomabechi, Keiko Honda, Mariko Ikeda, Noboru Ohsawa, Motoaki Wakiyama, Noriko Handa, Mikako Shirouzu, Teruki Honma, Akiko Tanaka, Shigeyuki Yokoyama

{"title":"Crystal structures of the S6K1 kinase domain in complexes with inhibitors.","authors":"Hideaki Niwa, Junko Mikuni, Shunta Sasaki, Yuri Tomabechi, Keiko Honda, Mariko Ikeda, Noboru Ohsawa, Motoaki Wakiyama, Noriko Handa, Mikako Shirouzu, Teruki Honma, Akiko Tanaka, Shigeyuki Yokoyama","doi":"10.1007/s10969-014-9188-8","DOIUrl":"https://doi.org/10.1007/s10969-014-9188-8","url":null,"abstract":"Ribosomal protein S6 kinase 1 (S6K1) is a serine/threonine protein kinase that plays an important role in the PIK3/mTOR signaling pathway, and is implicated in diseases including diabetes, obesity, and cancer. The crystal structures of the S6K1 kinase domain in complexes with staurosporine and the S6K1-specific inhibitor PF-4708671 have been reported. In the present study, five compounds (F108, F109, F176, F177, and F179) were newly identified by in silico screening of a chemical library and kinase assay. The crystal structures of the five inhibitors in complexes with the S6K1 kinase domain were determined at resolutions between 1.85 and 2.10 Å. All of the inhibitors bound to the ATP binding site, lying along the P-loop, while the activation loop stayed in the inactive form. Compound F179, with a carbonyl group in the middle of the molecule, altered the αC helix conformation by interacting with the invariant Lys123. Compounds F176 and F177 bound slightly distant from the hinge region, and their sulfoamide groups formed polar interactions with the protein. The structural features required for the specific binding of inhibitors are discussed.","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":" ","pages":"153-64"},"PeriodicalIF":0.0,"publicationDate":"2014-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9188-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32548127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Evaluation of intensity and pulse width of different moderators for designing a new diffractometer for protein crystals with large unit cells in J-PARC/MLF. J-PARC/MLF大细胞蛋白晶体衍射仪设计中不同缓冲剂的强度和脉宽评价

Journal of structural and functional genomics Pub Date : 2014-09-01 Epub Date: 2014-01-18 DOI: 10.1007/s10969-014-9170-5

Katsuaki Tomoyori, Katsuhiro Kusaka, Taro Yamada, Taro Tamada

{"title":"Evaluation of intensity and pulse width of different moderators for designing a new diffractometer for protein crystals with large unit cells in J-PARC/MLF.","authors":"Katsuaki Tomoyori, Katsuhiro Kusaka, Taro Yamada, Taro Tamada","doi":"10.1007/s10969-014-9170-5","DOIUrl":"https://doi.org/10.1007/s10969-014-9170-5","url":null,"abstract":"We plan to design a high-resolution biomacromolecule neutron time-of-flight diffractometer, which allows us to collect data from crystals with unit cells above 250 Å, in the materials and life science experimental facility at the Japan Proton Accelerator Research Complex. This new diffractometer can be used for a detailed analysis of large proteins such as membrane proteins and supermolecular complex. A quantitative comparison of the intensity and pulse width of a decoupled moderator (DM) against a coupled moderator (CM) considering the pulse width time resolution indicated that the DM satisfies the criteria for our diffractometer rather than the CM. The results suggested that a characteristic feature of the DM, i.e., narrow pulse width with a short tail, is crucial for the separation of Bragg reflections from crystals with large unit cells. On the other hand, it should be noted that the weak signals from the DM are buried under the high-level background caused by the incoherent scattering of hydrogen atoms, especially, in the case of large unit cells. We propose a profile-fitting integration method combined with the energy loss functions and a background subtraction method achieved by employing the statistics-sensitive nonlinear iterative peak-clipping algorithm. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":" ","pages":"131-5"},"PeriodicalIF":0.0,"publicationDate":"2014-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9170-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32043797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4