Journal of structural and functional genomics最新文献_第5页

Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin. 克拉多菌素抑制疟原虫赖氨酸- trna合成酶的结构基础。

Journal of structural and functional genomics Pub Date : 2014-06-01 Epub Date: 2014-06-17 DOI: 10.1007/s10969-014-9182-1

Sameena Khan, Arvind Sharma, Hassan Belrhali, Manickam Yogavel, Amit Sharma

{"title":"Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin.","authors":"Sameena Khan, Arvind Sharma, Hassan Belrhali, Manickam Yogavel, Amit Sharma","doi":"10.1007/s10969-014-9182-1","DOIUrl":"https://doi.org/10.1007/s10969-014-9182-1","url":null,"abstract":"Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9182-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32430255","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: 53

The crystal structure of pyrimidine/thiamin biosynthesis precursor-like domain-containing protein CAE31940 from proteobacterium Bordetella bronchiseptica RB50, and evolutionary insight into the NMT1/THI5 family. 博德氏杆菌RB50中嘧啶/硫胺素生物合成前体样结构域蛋白CAE31940的晶体结构及其对NMT1/THI5家族的进化见解

Journal of structural and functional genomics Pub Date : 2014-06-01 Epub Date: 2014-06-08 DOI: 10.1007/s10969-014-9180-3

Jacek Bajor, Karolina L Tkaczuk, Maksymilian Chruszcz, Hutton Chapman, Olga Kagan, Alexei Savchenko, Wladek Minor

引用次数: 0

Principal components analysis of protein sequence clusters. 蛋白质序列簇的主成分分析。

Journal of structural and functional genomics Pub Date : 2014-03-01 Epub Date: 2014-02-05 DOI: 10.1007/s10969-014-9173-2

Bo Wang, Michael A Kennedy

{"title":"Principal components analysis of protein sequence clusters.","authors":"Bo Wang, Michael A Kennedy","doi":"10.1007/s10969-014-9173-2","DOIUrl":"https://doi.org/10.1007/s10969-014-9173-2","url":null,"abstract":"Sequence analysis of large protein families can produce sub-clusters even within the same family. In some cases, it is of interest to know precisely which amino acid position variations are most responsible for driving separation into sub-clusters. In large protein families composed of large proteins, it can be quite challenging to assign the relative importance to specific amino acid positions. Principal components analysis (PCA) is ideal for such a task, since the problem is posed in a large variable space, i.e. the number of amino acids that make up the protein sequence, and PCA is powerful at reducing the dimensionality of complex problems by projecting the data into an eigenspace that represents the directions of greatest variation. However, PCA of aligned protein sequence families is complicated by the fact that protein sequences are traditionally represented by single letter alphabetic codes, whereas PCA of protein sequence families requires conversion of sequence information into a numerical representation. Here, we introduce a new amino acid sequence conversion algorithm optimized for PCA data input. The method is demonstrated using a small artificial dataset to illustrate the characteristics and performance of the algorithm, as well as a small protein sequence family consisting of nine members, COG2263, and finally with a large protein sequence family, Pfam04237, which contains more than 1,800 sequences that group into two sub-clusters. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9173-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32089747","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: 21

Carboxylic acids in crystallization of macromolecules: learning from successful crystallization experiments. 大分子结晶中的羧酸:从成功的结晶实验中学习。

Journal of structural and functional genomics Pub Date : 2014-03-01 Epub Date: 2014-01-23 DOI: 10.1007/s10969-014-9171-4

Lesa R Offermann, John Z He, Nicholas J Mank, William T Booth, Maksymilian Chruszcz

{"title":"Carboxylic acids in crystallization of macromolecules: learning from successful crystallization experiments.","authors":"Lesa R Offermann, John Z He, Nicholas J Mank, William T Booth, Maksymilian Chruszcz","doi":"10.1007/s10969-014-9171-4","DOIUrl":"https://doi.org/10.1007/s10969-014-9171-4","url":null,"abstract":"The production of macromolecular crystals suitable for structural analysis is one of the most important and limiting steps in the structure determination process. Often, preliminary crystallization trials are performed using hundreds of empirically selected conditions. Carboxylic acids and/or their salts are one of the most popular components of these empirically derived crystallization conditions. Our findings indicate that almost 40 % of entries deposited to the Protein Data Bank (PDB) reporting crystallization conditions contain at least one carboxylic acid. In order to analyze the role of carboxylic acids in macromolecular crystallization, a large-scale analysis of the successful crystallization experiments reported to the PDB was performed. The PDB is currently the largest source of crystallization data, however it is not easily searchable. These complications are due to a combination of a free text format, which is used to capture information on the crystallization experiments, and the inconsistent naming of chemicals used in crystallization experiments. Despite these difficulties, our approach allows for the extraction of over 47,000 crystallization conditions from the PDB. Initially, the selected conditions were investigated to determine which carboxylic acids or their salts are most often present in crystallization solutions. From this group, selected sets of crystallization conditions were analyzed in detail, assessing parameters such as concentration, pH, and precipitant used. Our findings will lead to the design of new crystallization screens focused around carboxylic acids. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9171-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32054139","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

Structural characterization of a hypothetical protein: a potential agent involved in trimethylamine metabolism in Catenulispora acidiphila. 一种假想蛋白质的结构特征:一种参与嗜酸链孢三甲胺代谢的潜在因子。

Journal of structural and functional genomics Pub Date : 2014-03-01 Epub Date: 2014-02-22 DOI: 10.1007/s10969-014-9176-z

Ekaterina V Filippova, Chi-Hao Luan, Sara F Dunne, Olga Kiryukhina, George Minasov, Ludmilla Shuvalova, Wayne F Anderson

{"title":"Structural characterization of a hypothetical protein: a potential agent involved in trimethylamine metabolism in Catenulispora acidiphila.","authors":"Ekaterina V Filippova, Chi-Hao Luan, Sara F Dunne, Olga Kiryukhina, George Minasov, Ludmilla Shuvalova, Wayne F Anderson","doi":"10.1007/s10969-014-9176-z","DOIUrl":"https://doi.org/10.1007/s10969-014-9176-z","url":null,"abstract":"Catenulispora acidiphila is a newly identified lineage of actinomycetes that produces antimicrobial activities and represents a promising source of novel antibiotics and secondary metabolites. Among the discovered protein coding genes, 68 % were assigned a putative function, while the remaining 32 % are genes encoding \"hypothetical\" proteins. Caci_0382 is one of the \"hypothetical\" proteins that has very few homologs. Sequence analysis shows that the protein belongs to the NTF2-like protein family. The structure of Caci_0382 demonstrates that it shares the same fold and has a similar active site as limonene-1,2-epoxide hydrolase, which suggests that it may have a related function. Using a fluorescence thermal shift assay, we identified stabilizing compounds that suggest potential natural ligands of Caci_0382. Using this information, we determined the crystal structure in complex with trimethylamine to provide a better understanding of the function of this uncharacterized protein. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9176-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32146925","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: 6

Complete backbone and DENQ side chain NMR assignments in proteins from a single experiment: implications to structure-function studies. 完整的主链和DENQ侧链核磁共振分配在蛋白质从一个单一的实验:对结构功能研究的影响。

Journal of structural and functional genomics Pub Date : 2014-03-01 Epub Date: 2014-02-18 DOI: 10.1007/s10969-014-9175-0

Jithender G Reddy, Ramakrishna V Hosur

{"title":"Complete backbone and DENQ side chain NMR assignments in proteins from a single experiment: implications to structure-function studies.","authors":"Jithender G Reddy, Ramakrishna V Hosur","doi":"10.1007/s10969-014-9175-0","DOIUrl":"https://doi.org/10.1007/s10969-014-9175-0","url":null,"abstract":"Resonance assignment is the first and the most crucial step in all nuclear magnetic resonance (NMR) investigations on structure-function relationships in biological macromolecules. Often, the assignment exercise has to be repeated several times when specific interactions with ligands, substrates etc., have to be elucidated for understanding the functional mechanisms. While the protein backbone serves to provide a scaffold, the side chains interact directly with the ligands. Such investigations will be greatly facilitated, if there are rapid methods for obtaining exhaustive information with minimum of NMR experimentation. In this context, we present here a pulse sequence which exploits the recently introduced technique of parallel detection of multiple nuclei, e.g. (1)H and (13)C, and results in two 3D-data sets simultaneously. These yield complete backbone resonance assignment ((1)H(N), (15)N, (13)CO, (1)Hα/(13)Cα, and (1)Hβ/(13)Cβ chemical shifts) and side chain assignment of D, E, N and Q residues. Such an exhaustive assignment has the potential of yielding accurate 3D structures using one or more of several algorithms which calculate structures of the molecules very reliably on the basis of NMR chemical shifts alone. The side chain assignments of D, E, N, and Q will be extremely valuable for interaction studies with different ligands; D and E side chains are known to be involved in majority of catalytic activities. Utility of this experiment has been demonstrated with Ca(2+) bound M-crystallin, which contains largely D, E, N and Q residues at the metal binding sites. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-014-9175-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32130206","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: 6

Arabinose 5-phosphate covalently inhibits transaldolase. 阿拉伯糖5-磷酸共价抑制转醛缩酶。

Journal of structural and functional genomics Pub Date : 2014-03-01 Epub Date: 2014-02-09 DOI: 10.1007/s10969-014-9174-1

Samuel H Light, Wayne F Anderson

引用次数: 8

The crystal structure of sterol carrier protein 2 from Yarrowia lipolytica and the evolutionary conservation of a large, non-specific lipid-binding cavity. 脂质体耶氏菌甾醇载体蛋白2的晶体结构及一个大型非特异性脂质结合腔的进化保护

Journal of structural and functional genomics Pub Date : 2013-12-01 Epub Date: 2013-11-17 DOI: 10.1007/s10969-013-9166-6

Federico Perez De Berti, Stefano Capaldi, Raúl Ferreyra, Noelia Burgardt, Juan P Acierno, Sebastián Klinke, Hugo L Monaco, Mario R Ermácora

{"title":"The crystal structure of sterol carrier protein 2 from Yarrowia lipolytica and the evolutionary conservation of a large, non-specific lipid-binding cavity.","authors":"Federico Perez De Berti, Stefano Capaldi, Raúl Ferreyra, Noelia Burgardt, Juan P Acierno, Sebastián Klinke, Hugo L Monaco, Mario R Ermácora","doi":"10.1007/s10969-013-9166-6","DOIUrl":"https://doi.org/10.1007/s10969-013-9166-6","url":null,"abstract":"Sterol carrier protein 2 (SCP2), a small intracellular domain present in all forms of life, binds with high affinity a broad spectrum of lipids. Due to its involvement in the metabolism of long-chain fatty acids and cholesterol uptake, it has been the focus of intense research in mammals and insects; much less characterized are SCP2 from other eukaryotic cells and microorganisms. We report here the X-ray structure of Yarrowia lipolytica SCP2 (YLSCP2) at 2.2 Å resolution in complex with palmitic acid. This is the first fungal SCP2 structure solved, and it consists of the canonical five-stranded β-sheet covered on the internal face by a layer of five α-helices. The overall fold is conserved among the SCP2 family, however, YLSCP2 is most similar to the SCP2 domain of human MFE-2, a bifunctional enzyme acting on peroxisomal β-oxidation. We have identified the common structural elements defining the shape and volume of the large binding cavity in all species characterized. Moreover, we found that the cavity of the SCP2 domains is distinctly formed by carbon atoms, containing neither organized water nor rigid polar interactions with the ligand. These features are in contrast with those of fatty acid binding proteins, whose internal cavities are more polar and contain bound water. The results will help to design experiments to unveil the SCP2 function in very different cellular contexts and metabolic conditions.","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-013-9166-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31872923","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: 10

New LIC vectors for production of proteins from genes containing rare codons. 用于从含有稀有密码子的基因中生产蛋白质的新型 LIC 载体。

Journal of structural and functional genomics Pub Date : 2013-12-01 Epub Date: 2013-09-22 DOI: 10.1007/s10969-013-9163-9

William H Eschenfeldt, Magdalena Makowska-Grzyska, Lucy Stols, Mark I Donnelly, Robert Jedrzejczak, Andrzej Joachimiak

{"title":"New LIC vectors for production of proteins from genes containing rare codons.","authors":"William H Eschenfeldt, Magdalena Makowska-Grzyska, Lucy Stols, Mark I Donnelly, Robert Jedrzejczak, Andrzej Joachimiak","doi":"10.1007/s10969-013-9163-9","DOIUrl":"10.1007/s10969-013-9163-9","url":null,"abstract":"In the effort to produce proteins coded by diverse genomes, structural genomics projects often must express genes containing codons that are rare in the production strain. To address this problem, genes expressing tRNAs corresponding to those codons are typically coexpressed from a second plasmid in the host strain, or from genes incorporated into production plasmids. Here we describe the modification of a series of LIC pMCSG vectors currently used in the high-throughput (HTP) production of proteins to include crucial tRNA genes covering rare codons for Arg (AGG/AGA) and Ile (AUA). We also present variants of these new vectors that allow analysis of ligand binding or co-expression of multiple proteins introduced through two independent LIC steps. Additionally, to accommodate the cloning of multiple large proteins, the size of the plasmids was reduced by approximately one kilobase through the removal of non-essential DNA from the base vector. Production of proteins from core vectors of this series validated the desired enhanced capabilities: higher yields of proteins expressed from genes with rare codons occurred in most cases, biotinylated derivatives enabled detailed automated ligand binding analysis, and multiple proteins introduced by dual LIC cloning were expressed successfully and in near balanced stoichiometry, allowing tandem purification of interacting proteins. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933008/pdf/nihms-526563.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751820","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: 0

Solution NMR structure of CD1104B from pathogenic Clostridium difficile reveals a distinct α-helical architecture and provides first structural representative of protein domain family PF14203. 致病性艰难梭菌CD1104B的溶液核磁共振结构揭示了一个独特的α-螺旋结构，并提供了蛋白结构域家族PF14203的第一个结构代表。

Journal of structural and functional genomics Pub Date : 2013-12-01 Epub Date: 2013-09-19 DOI: 10.1007/s10969-013-9164-8

Surya V S R K Pulavarti, Alexander Eletsky, Hsiau-Wei Lee, Thomas B Acton, Rong Xiao, John K Everett, James H Prestegard, Gaetano T Montelione, Thomas Szyperski

{"title":"Solution NMR structure of CD1104B from pathogenic Clostridium difficile reveals a distinct α-helical architecture and provides first structural representative of protein domain family PF14203.","authors":"Surya V S R K Pulavarti, Alexander Eletsky, Hsiau-Wei Lee, Thomas B Acton, Rong Xiao, John K Everett, James H Prestegard, Gaetano T Montelione, Thomas Szyperski","doi":"10.1007/s10969-013-9164-8","DOIUrl":"https://doi.org/10.1007/s10969-013-9164-8","url":null,"abstract":"A high-quality structure of the 68-residue protein CD1104B from Clostridium difficile strain 630 exhibits a distinct all α-helical fold. The structure presented here is the first representative of bacterial protein domain family PF14203 (currently 180 members) of unknown function (DUF4319) and reveals that the side-chains of the only two strictly conserved residues (Glu 8 and Lys 48) form a salt bridge. Moreover, these two residues are located in the vicinity of the largest surface cleft which is predicted to contribute to a surface area involved in protein-protein interactions. This, along with its coding in transposon CTn4, suggests that CD1104B (and very likely all members of Pfam 14203) functions by interacting with other proteins required for the transfer of transposons between different bacterial species. ","PeriodicalId":73957,"journal":{"name":"Journal of structural and functional genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10969-013-9164-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31744224","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: 1