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ClpP

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https://www.readbyqxmd.com/read/28924169/the-clpxp-protease-is-dispensable-for-degradation-of-unfolded-proteins-in-staphylococcus-aureus
#1
Steen G Stahlhut, Abdulelah A Alqarzaee, Camilla Jensen, Niclas S Fisker, Ana R Pereira, Mariana G Pinho, Vinai Chittezham Thomas, Dorte Frees
In living cells intracellular proteolysis is crucial for protein homeostasis, and ClpP proteases are conserved between eubacteria and the organelles of eukaryotic cells. In Staphylococcus aureus, ClpP associates to the substrate specificity factors, ClpX and ClpC forming two ClpP proteases, ClpXP and ClpCP. To address how individual ClpP proteases impact cell physiology, we constructed a S. aureus mutant expressing ClpX with an I265E substitution in the ClpP recognition tripeptide of ClpX. This mutant cannot degrade established ClpXP substrates confirming that the introduced amino acid substitution abolishes ClpXP activity...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922556/structure-and-mechanism-of-the-monoterpene-cyclolavandulyl-diphosphate-synthase-that-catalyses-consecutive-condensation-and-cyclisation
#2
Tomohisa Kuzuyama, Takeo Tomita, Masaya Kobayashi, Yuma Karita, Yoko Yasuno, Tetsuro Shinada, Makoto Nishiyama
Here, we report the three-dimensional structure of cyclolavandulyl diphosphate (CLPP) synthase (CLDS), which consecutively catalyses the condensation of two molecules of dimethylallyl diphosphate (DMAPP) followed by cyclisation to form a cyclic monoterpene, CLPP. The structures of apo-CLDS and CLDS in complex with Tris, pyrophosphate, and Mg2+ ion were refined at 2.00 Å resolution and 1.73 Å resolution, respectively. CLDS adopts a typical fold for cis-prenyl synthases and forms a homo-dimeric structure. An in vitro reaction using a regiospecifically 2H-substituted DMAPP substrate revealed the intramolecular proton transfer mechanism of the CLDS reaction...
September 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28917450/a-novel-class-of-plasmodial-clpp-protease-inhibitors-as-potential-antimalarial-agents
#3
Sourabh Mundra, Vandana Thakur, Angelica M Bello, Sumit Rathore, Mohd Asad, Lianhu Wei, Jane Yang, Sai Kumar Chakka, Radhakrishnan Mahesh, Pawan Malhotra, Asif Mohmmed, Lakshmi P Kotra
The prokaryotic ATP-dependent ClpP protease, localized in the relict plastid of malaria parasite, represents a potential drug target. In the present study, we utilized in silico structure-based screening and medicinal chemistry approaches to identify a novel pyrimidine series of compounds inhibiting P. falciparum ClpP protease activity and evaluated their antiparasitic activities. Structure-activity relationship indicated that morpholine moiety at C2, an aromatic substitution at N3 and a 4-oxo moiety on the pyrimidine are important for potent inhibition of ClpP enzyme along with antiparasiticidal activity...
September 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28910721/an-amino-acid-domino-effect-orchestrates-clpp-s-conformational-states
#4
REVIEW
Matthias Stahl, Stephan A Sieber
Maintaining the cellular protein homeostasis means managing life on the brink of death. This balance is largely based on precise fine-tuning of enzyme activities. For instance, the ClpP protease possesses several conformational switches which are fundamental to regulating its activity. Efforts have focused on revealing the structural basis of ClpP's conformational control. In the last decade, several amino acid clusters have been identified and functionally linked to specific activation states. Researchers have now begun to couple these hotspots to one another, uncovering a global network of residues that switch in response to internal and external stimuli...
September 11, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28882736/gene-centric-metegenome-analysis-reveals-diversity-of-pseudomonas-aeruginosa-biofilm-gene-orthologs-in-fresh-water-ecosystem
#5
Rani Anupama, Amitava Mukherjee, Subramanian Babu
Metagenomic analysis of biofilm forming bacteria in environmental samples remains challenging due to the non-availability of gene sequences of most of the uncultivable bacteria. Sequences of Pseudomonas aeruginosa PAO1-UW genes involved either directly or indirectly in biofilm formation were analyzed using BLASTn to obtain matching sequences from different strain, species and genus. Conserved regions in the functional domain of the amino acid sequences were used to design common primers for direct PCR analysis of freshwater metagenomes...
September 4, 2017: Genomics
https://www.readbyqxmd.com/read/28854633/contrasting-patterns-of-nucleotide-substitution-rates-provide-insight-into-dynamic-evolution-of-plastid-and-mitochondrial-genomes-of-geranium
#6
Seongjun Park, Tracey A Ruhlman, Mao-Lun Weng, Nahid H Hajrah, Jamal S M Sabir, Robert K Jansen
Geraniaceae have emerged as a model system for investigating the causes and consequences of variation in plastid and mitochondrial genomes. Incredible structural variation in plastid genomes (plastomes) and highly accelerated evolutionary rates have been reported in selected lineages and functional groups of genes in both plastomes and mitochondrial genomes (mitogenomes), and these phenomena have been implicated in cytonuclear incompatibility. Previous organelle genome studies have included limited sampling of Geranium, the largest genus in the family with over 400 species...
June 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28814717/drosophila-protease-clpxp-specifically-degrades-dmlrpprc1-controlling-mitochondrial-mrna-and-translation
#7
Yuichi Matsushima, Yuta Hirofuji, Masamune Aihara, Song Yue, Takeshi Uchiumi, Laurie S Kaguni, Dongchon Kang
ClpXP is the major protease in the mitochondrial matrix in eukaryotes, and is well conserved among species. ClpXP is composed of a proteolytic subunit, ClpP, and a chaperone-like subunit, ClpX. Although it has been proposed that ClpXP is required for the mitochondrial unfolded protein response, additional roles for ClpXP in mitochondrial biogenesis are unclear. Here, we found that Drosophila leucine-rich pentatricopeptide repeat domain-containing protein 1 (DmLRPPRC1) is a specific substrate of ClpXP. Depletion or introduction of catalytically inactive mutation of ClpP increases DmLRPPRC1 and causes non-uniform increases of mitochondrial mRNAs, accumulation of some unprocessed mitochondrial transcripts, and modest repression of mitochondrial translation in Drosophila Schneider S2 cells...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800729/accd-nuclear-transfer-of-platycodon-grandiflorum-and-the-plastid-of-early-campanulaceae
#8
Chang Pyo Hong, Jihye Park, Yi Lee, Minjee Lee, Sin Gi Park, Yurry Uhm, Jungho Lee, Chang-Kug Kim
BACKGROUND: Campanulaceae species are known to have highly rearranged plastid genomes lacking the acetyl-CoA carboxylase (ACC) subunit D gene (accD), and instead have a nuclear (nr)-accD. Plastid genome information has been thought to depend on studies concerning Trachelium caeruleum and genome announcements for Adenophora remotiflora, Campanula takesimana, and Hanabusaya asiatica. RNA editing information for plastid genes is currently unavailable for Campanulaceae. To understand plastid genome evolution in Campanulaceae, we have sequenced and characterized the chloroplast (cp) genome and nr-accD of Platycodon grandiflorum, a basal member of Campanulaceae...
August 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28799020/from-discovery-of-the-chop-axis-and-targeting-clpp-to-the-identification-of-additional-axes-of-the-uprmt-driven-by-the-estrogen-receptor-and-sirt3
#9
Timothy C Kenny, Doris Germain
The mitochondrial UPR (UPR(mt)) is rapidly gaining attention. While most studies on the UPR(mt) have focused on its role in aging, emerging studies suggest an important role of the UPR(mt) in cancer. Further, several of the players of the UPR(mt) in mammalian cells have well reported roles in the maintenance of the organelle. The goal of this review is to emphasize aspects of the UPR(mt) that have been overlooked in the current literature, describe the role of specific players of the UPR(mt) in the biology of the mitochondria and highlight the intriguing possibility that targeting the UPR(mt) in cancer may be already within reach...
August 10, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28751741/soil-microbial-community-structure-and-catabolic-activity-are-significantly-degenerated-in-successive-rotations-of-chinese-fir-plantations
#10
Zeyan Wu, Jianjuan Li, Jie Zheng, Jinfu Liu, Shuying Liu, Wenxiong Lin, Chengzhen Wu
This study examined the hypotheses that soil microbial community composition and catabolic activity would significantly degenerated by consecutive monoculture in Chinese fir plantations. The phospholipid fatty acids (PLFA) and community level physiological profiles (CLPP) methods were used to assess the variations of soil microbial community among the first rotation Chinese fir plantation (FCP), the second rotation plantation (SCP) and the third rotation plantation (TCP). The total content of PLFA biomarkers was highest in FCP, followed by SCP, and TCP was the least detected...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28748570/lichen-planopilaris-in-a-latin-american-chilean-population-demographics-clinical-profile-and-treatment-experience
#11
F Mardones, J Shapiro
BACKGROUND: Lichen planopilaris (LPP) is characterized by lymphocytic infiltrate, fibrosis and potential destruction of the hair follicle. Demographic and clinical studies in LPP are limited, and racial differences have not been thoroughly investigated. AIM: To analyse epidemiological data and clinical profiles of Chilean adults with LPP, and report on the treatments used. METHODS: This was a retrospective review of medical records and clinical follow-up of Chilean adults with a clinical and histopathological diagnosis of LPP...
July 27, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28731202/on-the-brink-the-highly-reduced-plastomes-of-nonphotosynthetic-ericaceae
#12
Thomas W A Braukmann, Michael B Broe, Saša Stefanović, John V Freudenstein
Ericaceae (the heather family) is a large and diverse group of plants that forms elaborate symbiotic relationships with mycorrhizal fungi, and includes several nonphotosynthetic lineages. Using an extensive sample of fully mycoheterotrophic (MH) species, we explored inter- and intraspecific variation as well as selective constraints acting on the plastomes of these unusual plants. The plastomes of seven MH genera were analysed in a phylogenetic context with two geographically disparate individuals sequenced for Allotropa, Monotropa, and Pityopus...
July 21, 2017: New Phytologist
https://www.readbyqxmd.com/read/28707598/protein-tagging-destruction-and-infection
#13
Chetana Bhaskarla, Manoj Bhosale, Pip Banerjee, Nagasuma Chandra, Dipankar Nandi
Cells possess protein quality control mechanisms to maintain proper cellular homeostasis. In eukaryotes, the roles of the ubiquitination and proteasome-mediated degradation of cellular proteins is well established. Recent studies have elucidated protein tagging mechanisms in prokaryotes, involving transfer messenger RNA (tmRNA) and pupylation. In this review, newer insights and bioinformatics analysis of two distinct bacterial protein tagging machineries are discussed. The machinery for tmRNA-mediated tagging is present in several eubacterial representatives, e...
July 13, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28698145/increase-in-proteins-involved-in-mitochondrial-fission-mitophagy-proteolysis-and-antioxidant-response-in-type-i-endometrial-cancer-as-an-adaptive-response-to-respiratory-complex-i-deficiency
#14
Antonella Cormio, Clara Musicco, Giuseppe Gasparre, Gennaro Cormio, Vito Pesce, Anna Maria Sardanelli, Maria Nicola Gadaleta
Pathogenic mtDNA mutations associated with alterations of respiratory complex I, mitochondrial proliferation (oncocytic-like phenotype) and increase in antioxidant response were previously reported in type I endometrial carcinoma (EC). To evaluate whether in the presence of pathogenic mtDNA mutations other mitochondrial adaptive processes are triggered by cancer cells, the expression level of proteins involved in mitochondrial dynamics, mitophagy, proteolysis and apoptosis were evaluated in type I ECs harboring pathogenic mtDNA mutations and complex I deficiency...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28681284/microbial-biodiversity-of-meadows-under-different-modes-of-land-use-catabolic-and-genetic-fingerprinting
#15
Agnieszka Wolinska, Magdalena Frąc, Karolina Oszust, Anna Szafranek-Nakonieczna, Urszula Zielenkiewicz, Zofia Stępniewska
The main goal of the study was to find differences in the bacterial community structure resulting from different ways of meadow management in order to get the first insight into microbial biodiversity in meadow samples. The next generation sequencing technique (454-pyrosequencing) was accompanied with the community level physiological profiling (CLPP) method in order to acquire combined knowledge of both genetic and catabolic bacterial fingerprinting of two studied meadows (hayland and pasture). Soil samples (FAO: Mollic Gleysol) were taken in April 2015 from the surface layer (0-20 cm)...
August 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28674070/bacillus-subtilis-intramembrane-protease-rasp-activity-in-escherichia-coli-and-in-vitro
#16
Daniel Parrell, Yang Zhang, Sandra Olenic, Lee Kroos
RasP is a predicted intramembrane metalloprotease of Bacillus subtilis that has been proposed to cleave the stress response anti-sigma factors RsiW and RsiV, the cell division protein FtsL, and remnant signal peptides within their transmembrane segments. To provide evidence for direct effects of RasP on putative substrates, we developed a heterologous coexpression system. Since expression of catalytically inactive RasP E21A inhibited expression of other membrane proteins in Escherichia coli, we added extra transmembrane segments to RasP E21A, which allowed accumulation of most other membrane proteins...
October 1, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28666467/the-metabolic-footprint-of-the-airway-bacterial-community-in-cystic-fibrosis
#17
Vaishnavi Narayanamurthy, John M Sweetnam, Darcy R Denner, Lena W Chen, Edward T Naureckas, Bharathi Laxman, Steven R White
BACKGROUND: Progressive, chronic bacterial infection of the airways is a leading cause of death in cystic fibrosis (CF). Culture-independent methods based on sequencing of the bacterial 16S rRNA gene describe a distinct microbial community that decreases in richness and diversity with disease progression. Understanding the functional characteristics of the microbial community may aid in identifying potential therapies and may assist in management, but current methods are cumbersome. Here, we demonstrate the use of an oxidative metabolic assay as a complement to sequencing methods to describe the microbiome in the airways of patients with CF...
June 30, 2017: Microbiome
https://www.readbyqxmd.com/read/28629725/relationship-between-histopathological-status-of-the-helicobacter-pylori-infected-patients-and-proteases-of-h-%C3%A2-pylori-in-isolates-carrying-diverse-virulence-genotypes
#18
Somayyeh Gharibi, Tahereh Falsafi, Masoud Alebouyeh, Nastaran Farzi, Farzam Vaziri, Mohamad Reza Zali
Helicobacter pylori is the main cause of several gastroduodenal diseases in Humans. Among various virulence factors of H. pylori, proteases may also be involved in its pathogenicity. In this study, relationship between proteolytic activity of H. pylori strains and histopathological changes of the stomach was investigated in the patients infected with strains carrying diverse virulence factors. H. pylori strains were isolated from the biopsies of 116 patients who referred to hospital for their gastroduodenal disorders, in Tehran, Iran...
June 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28625996/natural-dna-transformation-is-functional-in-lactococcus-lactis-ssp-cremoris-kw2
#19
Blandine David, Amandine Radziejwoski, Frédéric Toussaint, Laetitia Fontaine, Marie Henry de Frahan, Cédric Patout, Sabine van Dillen, Patrick Boyaval, Philippe Horvath, Christophe Fremaux, Pascal Hols
Lactococcus lactis is one of the most commonly used lactic acid bacteria in the dairy industry. Activation of competence for natural DNA transformation in this species would greatly improve the selection of novel strains with desired genetic traits. Here, we investigated the activation of natural transformation in L. lactis ssp. cremoris KW2, a strain of plant origin whose genome encodes the master competence regulator ComX and the complete set of proteins usually required for natural transformation. In the absence of knowledge about competence regulation in this species, we constitutively overproduced ComX in a reporter strain of late competence phase activation and showed, by transcriptomic analyses, a ComX-dependent induction of all key competence genes...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28619145/thymol-kills-bacteria-reduces-biofilm-formation-and-protects-mice-against-a-fatal-infection-of-actinobacillus-pleuropneumoniae-strain-l20
#20
Lei Wang, Xueqin Zhao, Chunling Zhu, Xiaojing Xia, Wanhai Qin, Mei Li, Tongzhao Wang, Shijun Chen, Yanzhao Xu, Bolin Hang, Yawei Sun, Jinqing Jiang, Langford Paul Richard, Liancheng Lei, Gaiping Zhang, Jianhe Hu
Actinobacillus pleuropneumoniae is the causative agent of the highly contagious and deadly respiratory infection porcine pleuropneumonia, resulting in serious losses to the pig industry worldwide. Alternative to antibiotics are urgently needed due to the serious increase in antimicrobial resistance. Thymol is a monoterpene phenol and efficiently kills a variety of bacteria. This study found that thymol has strong bactericidal effects on the A. pleuropneumoniae 5b serotype strain, an epidemic strain in China...
May 2017: Veterinary Microbiology
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