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https://www.readbyqxmd.com/read/28895719/radical-sam-enzymes-involved-in-ripp-biosynthesis
#1
Nilkamal Mahanta, Graham A Hudson, Douglas A Mitchell
Ribosomally synthesized and post-translationally modified peptides (RiPPs) display a diverse range of structures and continue to expand as a natural product class. Accordingly, RiPPs exhibit a wide array of bioactivities, such as broad and narrow spectrum growth suppressors, antidiabetics, as well as antinociception and anticancer agents. Owing to these properties, and the complex repertoire of post-translational modifications (PTMs) that give rise to these molecules, RiPP biosynthesis has been intensely studied...
September 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28893989/structures-of-the-peptide-modifying-radical-sam-enzyme-suib-elucidate-the-basis-of-substrate-recognition
#2
Katherine M Davis, Kelsey R Schramma, William A Hansen, John P Bacik, Sagar D Khare, Mohammad R Seyedsayamdost, Nozomi Ando
Posttranslational modification of ribosomally synthesized peptides provides an elegant means for the production of biologically active molecules known as RiPPs (ribosomally synthesized and posttranslationally modified peptides). Although the leader sequence of the precursor peptide is often required for turnover, the exact mode of recognition by the modifying enzymes remains unclear for many members of this class of natural products. Here, we have used X-ray crystallography and computational modeling to examine the role of the leader peptide in the biosynthesis of a homolog of streptide, a recently identified peptide natural product with an intramolecular lysine-tryptophan cross-link, which is installed by the radical S-adenosylmethionine (SAM) enzyme, StrB...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28891639/three-principles-of-diversity-generating-biosynthesis
#3
Wenjia Gu, Eric W Schmidt
Natural products are significant therapeutic agents and valuable drug leads. This is likely owing to their three-dimensional structural complexity, which enables them to form complex interactions with biological targets. Enzymes from natural product biosynthetic pathways show great potential to generate natural product-like compounds and libraries. Many challenges still remain in biosynthesis, such as how to rationally synthesize small molecules with novel structures and how to generate maximum chemical diversity...
September 11, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28859135/identification-of-mir-16-as-an-endogenous-reference-gene-for-the-normalization-of-urinary-exosomal-mirna-expression-data-from-ckd-patients
#4
Tim Lange, Sylvia Stracke, Rainer Rettig, Uwe Lendeckel, Jana Kuhn, Rabea Schlüter, Volkhard Rippe, Karlhans Endlich, Nicole Endlich
Chronic kidney disease (CKD) is a severe disorder with an increasing incidence worldwide. An early detection may help to prevent its progression and to minimize the risk of cardiovascular diseases as one of the major comorbidities. Recently, extracellular miRNAs like urinary exosomal miRNAs became of great interest as non-invasive biomarkers which can be determined by RT-qPCR. But until now, there is no consensus regarding the normalization of miRNAs isolated from body fluids. The present study analyzed the miRNAs miR-16, miR-92a, miR-21, miR-124a and the small nuclear RNA RNU6B for their applicability as an endogenous reference gene in expression studies of exosomal miRNAs isolated from CKD patients...
2017: PloS One
https://www.readbyqxmd.com/read/28846667/klebsazolicin-inhibits-70s-ribosome-by-obstructing-the-peptide-exit-tunnel
#5
Mikhail Metelev, Ilya A Osterman, Dmitry Ghilarov, Nelli F Khabibullina, Alexander Yakimov, Konstantin Shabalin, Irina Utkina, Dmitry Y Travin, Ekaterina S Komarova, Marina Serebryakova, Tatyana Artamonova, Mikhail Khodorkovskii, Andrey L Konevega, Petr V Sergiev, Konstantin Severinov, Yury S Polikanov
Whereas screening of the small-molecule metabolites produced by most cultivatable microorganisms often results in the rediscovery of known compounds, genome-mining programs allow researchers to harness much greater chemical diversity, and result in the discovery of new molecular scaffolds. Here we report the genome-guided identification of a new antibiotic, klebsazolicin (KLB), from Klebsiella pneumoniae that inhibits the growth of sensitive cells by targeting ribosomes. A ribosomally synthesized post-translationally modified peptide (RiPP), KLB is characterized by the presence of a unique N-terminal amidine ring that is essential for its activity...
October 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28843883/fatigue-strength-of-yttria-stabilized-zirconia-polycrystals-effects-of-grinding-polishing-glazing-and-heat-treatment
#6
Camila Pauleski Zucuni, Luís Felipe Guilardi, Marilia Pivetta Rippe, Gabriel Kalil Rocha Pereira, Luiz Felipe Valandro
This study aimed to evaluate and compare the effect of different surface post-processing treatments (polishing, heat treatment, glazing, polishing + heat treatment and polishing + glazing) on the superficial characteristics (micromorphology and roughness), phase transformation and fatigue strength of a Y-TZP ceramic ground with diamond bur. Discs of Y-TZP ceramic were manufactured (ISO:6872-2015; final dimensions of 15mm in diameter and 1.2 ± 0.2mm in thickness) and randomly allocated according to the surface condition: Ctrl - as-sintered; Gr - ground with coarse diamond bur; Gr+HT - ground and subjected to the heat treatment; Gr+Pol - ground and polished; Gr+Pol+HT - ground, polished and heat treated; Gr+Gl - ground and glazed; Gr+Pol+Gl - ground, polished and glazed...
June 15, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28829934/retentive-strength-of-y-tzp-crowns-comparison-of-different-silica-coating-methods-on-the-intaglio-surfaces
#7
V F Wandscher, C Prochnow, M P Rippe, L S Dorneles, G L Callegari, P Baldissara, R Scotti, L F Valandro
OBJECTIVE: To evaluate the effect of different methods of silica deposition on the intaglio surface of yttrium oxide stabilized zirconia polycrystal (Y-TZP) crowns on the retentive strength of the crowns. METHODS: One hundred simplified full-crown preparations produced from fiber-reinforced polymer material were scanned, and 100 Y-TZP crowns with occlusal retentions were milled. Crown/preparation assemblies were randomly allocated into five groups (n=20) according to the treatment of the intaglio surfaces: TBS = tribochemical silica coating via air-abrasion with 30-μm silica-coated alumina particles; GHF1 = application of thin glaze layer + hydrofluoric acid (HF) etching for 1 minute; GHF5 = glaze application + HF for 5 minutes; GHF15 = glaze application + HF for 15 minutes; NANO = silica nanofilm deposition (5 nm) via magnetron sputtering...
September 2017: Operative Dentistry
https://www.readbyqxmd.com/read/28796998/microrna-dependent-control-of-serotonin-induced-pulmonary-arterial-contraction
#8
Diana Dahan, Tran Thi Hien, Philip Tannenberg, Mari Ekman, Catarina Rippe, Thomas Boettger, Thomas Braun, Karin Tran-Lundmark, Phan-Kiet Tran, Karl Swärd, Sebastian Albinsson
BACKGROUND: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. METHODS: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. RESULTS: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced...
2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28715095/a-self-sacrificing-n-methyltransferase-is-the-precursor-of-the-fungal-natural-product-omphalotin
#9
Sascha Ramm, Bartlomiej Krawczyk, Agnes Mühlenweg, Annette Poch, Eva Mösker, Roderich D Süssmuth
Research on ribosomally synthesized and posttranslationally modified peptides (RiPPs) has led to an increasing understanding of biosynthetic mechanisms, mostly drawn from bacterial examples. In contrast, reports on RiPPs from fungal producers, apart from the amanitins and phalloidins, are still scarce. The fungal cyclopeptide omphalotin A carries multiple N-methylations on the peptide backbone, a modification previously known only from nonribosomal peptides. Mining the genome of the omphalotin-producing fungus for a precursor peptide led to the identification of two biosynthesis genes, one encoding a methyltransferase OphMA that catalyzes the automethylation of its C-terminus, which is then released and cyclized by the protease OphP...
July 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28704043/structural-insights-into-thioether-bond-formation-in-the-biosynthesis-of-sactipeptides
#10
Tyler L Grove, Paul M Himes, Sungwon Hwang, Hayretin Yumerefendi, Jeffrey B Bonanno, Brian Kuhlman, Steven C Almo, Albert A Bowers
Sactipeptides are ribosomally synthesized peptides that contain a characteristic thioether bridge (sactionine bond) that is installed posttranslationally and is absolutely required for their antibiotic activity. Sactipeptide biosynthesis requires a unique family of radical SAM enzymes, which contain multiple [4Fe-4S] clusters, to form the requisite thioether bridge between a cysteine and the α-carbon of an opposing amino acid through radical-based chemistry. Here we present the structure of the sactionine bond-forming enzyme CteB, from Clostridium thermocellum ATCC 27405, with both SAM and an N-terminal fragment of its peptidyl-substrate at 2...
August 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28691075/chimeric-leader-peptides-for-the-generation-of-non-natural-hybrid-ripp-products
#11
Brandon J Burkhart, Nidhi Kakkar, Graham A Hudson, Wilfred A van der Donk, Douglas A Mitchell
Combining biosynthetic enzymes from multiple pathways is an attractive approach for producing molecules with desired structural features; however, progress has been hampered by the incompatibility of enzymes from unrelated pathways and intolerance toward alternative substrates. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a diverse natural product class that employs a biosynthetic logic that is highly amenable to engineering new compounds. RiPP biosynthetic proteins modify their substrates by binding to a motif typically located in the N-terminal leader region of the precursor peptide...
June 28, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28682627/ribosomal-natural-products-tailored-to-fit
#12
Michael A Funk, Wilfred A van der Donk
Ribosomally synthesized and Post-translationally modified Peptides (RiPPs) take advantage of the ribosomal translation machinery to generate linear peptides that are subsequently modified with heterocycles and/or macrocycles to impose three-dimensional structure and thwart degradation by proteases. Although RiPP precursors are limited to proteinogenic amino acids, post-translational modifications (PTMs) can alter the structure of individual amino acids and thereby improve the stability and biological activity of the molecule...
July 18, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28678974/clinical-performance-and-failure-modes-of-pulpless-teeth-restored-with-posts-a-systematic-review
#13
REVIEW
Ana Maria Estivalete Marchionatti, Vinícius Felipe Wandscher, Marília Pivetta Rippe, Osvaldo Bazzan Kaizer, Luiz Felipe Valandro
The aim of this systematic review was to compare the clinical performance and failure modes of teeth restored with intra-radicular retainers. A search was performed on PubMed/Medline, Central and ClinicalTrials databases for randomized clinical trials comparing clinical behavior and failures of at least two types of retainers. From 341 detected papers, 16 were selected for full-text analysis, of which 9 met the eligibility criteria. A manual search added 2 more studies, totalizing 11 studies that were included in this review...
July 3, 2017: Brazilian Oral Research
https://www.readbyqxmd.com/read/28650175/bioactive-peptide-natural-products-as-lead-structures-for-medicinal-use
#14
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28634235/mechanistic-elucidation-of-the-mycofactocin-biosynthetic-radical-s-adenosylmethionine-protein-mftc
#15
Bulat Khaliullin, Richard Ayikpoe, Mason Tuttle, John A Latham
Ribosomally synthesized and posttranslationally modified peptide (RiPP) pathways produce a diverse array of natural products. A subset of these pathways depends on radical S-adenosylmethionine proteins to modify the RiPP-produced peptide. Mycofactocin biosynthesis is one example of an S-adenosylmethionine protein-dependent RiPP pathway. Recently, it has been shown that MftC catalyzes the oxidative decarboxylation of the C-terminal tyrosine (Tyr-30) on the mycofactocin precursor peptide MftA; however, this product has not been verified by techniques other than MS...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28623182/mygenefriends-a-social-network-linking-genes-genetic-diseases-and-researchers
#16
Alexis Allot, Kirsley Chennen, Yannis Nevers, Laetitia Poidevin, Arnaud Kress, Raymond Ripp, Julie Dawn Thompson, Olivier Poch, Odile Lecompte
BACKGROUND: The constant and massive increase of biological data offers unprecedented opportunities to decipher the function and evolution of genes and their roles in human diseases. However, the multiplicity of sources and flow of data mean that efficient access to useful information and knowledge production has become a major challenge. This challenge can be addressed by taking inspiration from Web 2.0 and particularly social networks, which are at the forefront of big data exploration and human-data interaction...
June 16, 2017: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/28608363/misynpat-an-integrated-knowledge-base-linking-clinical-genetic-and-structural-data-for-disease-causing-mutations-in-human-mitochondrial-aminoacyl-trna-synthetases
#17
Luc Moulinier, Raymond Ripp, Gaston Castillo, Olivier Poch, Marie Sissler
Numerous mutations in each of the mitochondrial aminoacyl-tRNA synthetases (aaRSs) have been implicated in human diseases. The mutations are autosomal and recessive and lead mainly to neurological disorders, although with pleiotropic effects. The processes and interactions that drive the etiology of the disorders associated with mitochondrial aaRSs (mt-aaRSs) are far from understood. The complexity of the clinical, genetic, and structural data requires concerted, interdisciplinary efforts to understand the molecular biology of these disorders...
June 12, 2017: Human Mutation
https://www.readbyqxmd.com/read/28606854/divergent-roles-of-the-drosophila-melanogaster-globins
#18
Thorsten Burmester, Agnes Wawrowski, Ines Diepenbruck, Katharina Schrick, Nina Seiwert, Fabian Ripp, Andreas Prothmann, Thomas Hankeln
In contrast to long-held assumptions, the gene repertoire of most insects includes hemoglobins. Analyses of the genome of the fruitfly Drosophila melanogaster identified three distinct hemoglobin genes (glob1, glob2, and glob3). While glob1 is predominantly associated with the tracheal system and fat body, glob2 and glob3 are almost exclusively expressed in the testis. The physiological role of globins in Drosophila is uncertain. Here, we studied the functions of the three globins in a cell culture system. Drosophila Schneider 2 (S2) cells were stably transfected with each of the three globins and the empty vector as control...
June 9, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28604729/dnmt-and-hdac-inhibitors-induce-cryptic-transcription-start-sites-encoded-in-long-terminal-repeats
#19
David Brocks, Christopher R Schmidt, Michael Daskalakis, Hyo Sik Jang, Nakul M Shah, Daofeng Li, Jing Li, Bo Zhang, Yiran Hou, Sara Laudato, Daniel B Lipka, Johanna Schott, Holger Bierhoff, Yassen Assenov, Monika Helf, Alzbeta Ressnerova, Md Saiful Islam, Anders M Lindroth, Simon Haas, Marieke Essers, Charles D Imbusch, Benedikt Brors, Ina Oehme, Olaf Witt, Michael Lübbert, Jan-Philipp Mallm, Karsten Rippe, Rainer Will, Dieter Weichenhan, Georg Stoecklin, Clarissa Gerhäuser, Christopher C Oakes, Ting Wang, Christoph Plass
Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions...
July 2017: Nature Genetics
https://www.readbyqxmd.com/read/28591521/changes-in-face-specific-neural-processing-explain-reduced-cuteness-and-approachability-of-infants-with-cleft-lip
#20
Renske Huffmeijer, Janna Eilander, Viara R Mileva-Seitz, Ralph C A Rippe
The current study investigated whether changes in the neural processing of faces of infants with a facial abnormality - a cleft lip - mediate effects of the cleft lip on judgments of infant cuteness and approachability. Event-related potentials (ERPs) in response to pictures of faces of healthy infants and infants with a cleft lip, and ratings of cuteness and approachability of these infant faces, were obtained from 30 females. Infants with a cleft lip were rated as less attractive (less cute and approachable) than healthy infants, and both the N170 and P2 components of the ERP were of reduced amplitude in response to pictures of infants with a cleft lip...
June 18, 2017: Social Neuroscience
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