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https://www.readbyqxmd.com/read/28817220/klk14-interactions-with-hai-1-and-hai-2-serine-protease-inhibitors-a-molecular-dynamics-and-relative-free-energy-calculations-study
#1
Christian Solís-Calero, Hernandes F Carvalho
Kallikrein 14 (KLK14) is a serine protease linked to several pathologies including prostate cancer and positively correlates with Gleason score. Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression. In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28816230/plasma-pcsk9-levels-are-unrelated-to-arterial-stiffness-in-a-community-based-4-8-year-prospective-study
#2
J Han, X Wang, P Ye, R Cao, X Yang, W Xiao, Y Zhang, Y Bai, H Wu
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important circulating serine protease in low-density lipoprotein cholesterol (LDL-C) metabolism. Increased plasma PCSK9 levels lead to increased plasma levels of LDL-C and an increased risk of cardiovascular disease (CVD). LDL-C is positively correlated with arterial stiffness, a surrogate endpoint of CVD. However, whether plasma levels of PCSK9 could influence arterial stiffness is still unclear. Our study examined the relationship between plasma levels of PCSK9 and arterial stiffness (carotid-femoral pulse wave velocity (cf-PWV)) in a community-based population...
August 17, 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28815968/discovery-of-naphthyl-n-acylhydrazone-p38%C3%AE-mapk-inhibitors-with-in-vivo-anti-inflammatory-and-anti-tnf-%C3%AE-activity
#3
Rosana H C N Freitas, Natália M Cordeiro, Patrícia R Carvalho, Marina A Alves, Isabella A Guedes, Tayna S Valerio, Laurent E Dardenne, Lídia M Lima, Eliezer J Barreiro, Patrícia D Fernandes, Carlos A M Fraga
Protein kinases constitute attractive therapeutic targets for development of new prototypes to treat different chronic diseases. Several available drugs, like tinibs, are tyrosine kinase inhibitors, meanwhile, inhibitors of serine/threonine kinases, such as mitogen-activated protein kinase (MAPK) are still trying to overcome some problems in one of the steps of clinical development to become drugs. So, here we reported the synthesis, the in vitro kinase inhibitory profile, docking studies and the evaluation of anti-inflammatory profile of new naphthyl-N-acylhydrazone derivatives using animal models...
August 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28815858/loss-of-chloroplast-localized-protein-phosphatase-2cs-in-arabidopsis-thaliana-leads-to-enhancement-of-the-plant-immunity-and-resistance-to-xanthomonas-campestris-pv-campestris-infection
#4
Chiharu Akimoto-Tomiyama, Shigeru Tanabe, Hideyuki Kajiwara, Eiichi Minami, Hirokazu Ochiai
Protein phosphatases (PPs) counteract kinases in reversible phosphorylation events during numerous signal transduction pathways in eukaryotes. PP2Cs, one of the four major classes of serine/threonine specific PPs family is greatly expanded in plants. Thus PP2C is thought to have a specific role in a signal transduction pathway. Some rice PP2Cs classified to subgroup K were responsive to the infection by the compatible Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight. In A. thaliana, orthologous PP2C genes (AtPP2C62 and AtPP2C26) classified to subgroup K were also responsive to Xanthomonas campestris pv...
August 16, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28815577/emerging-roles-of-rhomboid-like-pseudoproteases-in-inflammatory-and-innate-immune-responses
#5
REVIEW
Wei-Wei Luo, Hong-Bing Shu
Rhomboid-like pseudoproteases are a conserved superfamily of proteins related to rhomboid intramembrane serine proteases that lack key catalytic residues. iRhom2, a member of the rhomboid-like pseudoprotease superfamily, has been reported to regulate the maturation and trafficking of ADAM17, and be associated with inflammatory arthritis. Recent studies demonstrate that iRhom2 is also involved in innate immunity by regulating the trafficking and stability of MITA (also called STING), which is a central adaptor in innate antiviral signalling pathways...
August 17, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28815508/multipart-dna-assembly-using-site-specific-recombinases-from-the-large-serine-integrase-family
#6
Femi J Olorunniji, Christine Merrick, Susan J Rosser, Margaret C M Smith, W Marshall Stark, Sean D Colloms
Assembling multiple DNA fragments into functional plasmids is an important and often rate-limiting step in engineering new functions in living systems. Bacteriophage integrases are enzymes that carry out efficient recombination reactions between short, defined DNA sequences known as att sites. These DNA splicing reactions can be used to assemble large numbers of DNA fragments into a functional circular plasmid in a method termed serine integrase recombinational assembly (SIRA). The resulting DNA assemblies can easily be modified by further recombination reactions catalyzed by the same integrase in the presence of its recombination directionality factor (RDF)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815494/use-of-the-dice-dual-integrase-cassette-exchange-system
#7
Alfonso P Farruggio, Mital S Bhakta, Michele P Calos
When constructing transgenic cell lines via plasmid DNA integration, precise targeting to a desired genomic location is advantageous. It is also often advantageous to remove the bacterial backbone, since bacterial elements can lead to the epigenetic silencing of neighboring DNA. The least cumbersome method to remove the plasmid backbone is recombinase-mediated cassette exchange (RMCE). RMCE is accomplished by arranging recombinase sites in the genome and in a donor plasmid such that a recombinase can both integrate the donor plasmid and excise its bacterial backbone...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815458/backbone-and-side-chain-resonance-assignments-of-ca-2-4-calmodulin-bound-to-beta-calcineurin-a-cambd-peptide
#8
C Andrew Fowler, Maria F Núñez Hernandez, Susan E O'Donnell, Liping Yu, Madeline A Shea
Calcineurin (CaN) is a heterodimeric and highly conserved serine/threonine phosphatase (PP2B) that plays a critical role in coupling calcium signals to physiological processes including embryonic cardiac development, NF-AT-regulated gene expression in immune responses, and apoptosis. The catalytic subunit (CaNA) has three isoforms (α, β, and γ,) in humans and seven isoforms in Paramecium. In all eukaryotes, the EF-hand protein calmodulin (CaM) regulates CaN activity in a calcium-dependent manner. The N- and C-domains of CaM (CaMN and CaMC) recognize a CaM-binding domain (CaMBD) within an intrinsically disordered region of CaNA that precedes the auto-inhibitory domain (AID) of CaNA...
August 16, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28815423/backbone-and-side-chain-1-h-15-n-and-13-c-resonance-assignments-of-a-novel-staphylococcal-inhibitor-of-myeloperoxidase
#9
Nicoleta T Ploscariu, Alvaro I Herrera, Srinivas Jayanthi, Thallapuranam K Suresh Kumar, Brian V Geisbrecht, Om Prakash
The bacterium Staphylococcus aureus produces an array of anti-inflammatory molecules that prevent the innate immune system from recognizing it as a pathogen and clearing it from the host. In the acute phase of inflammation, our immune system relies on neutrophils to clear invading bacteria. Recently, novel classes of secreted proteins from S. aureus, including the Extracellular Adherence Protein (EAP) family (Stapels et al., Proc Natl Acad Sci USA 111:13187-13192, 2014) and the Staphylococcal Peroxidase Inhibitor (SPIN), (unpublished work) have been identified as highly selective inhibitors acting on Neutrophil Serine Proteases (NSPs) and myeloperoxidase (MPO) respectively...
August 16, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28814953/in-vitro-characterization-of-jellyfish-venom-fibrin-ogen-olytic-enzymes-from-nemopilema-nomurai
#10
Seong Kyeong Bae, Hyunkyoung Lee, Yunwi Heo, Min Jung Pyo, Indu Choudhary, Chang Hoon Han, Won Duk Yoon, Changkeun Kang, Euikyung Kim
BACKGROUND: Because jellyfish are capable of provoking envenomation in humans, they are considered hazardous organisms. Although the effects of their toxins are a matter of concern, information on the venom components, biological activity and pathological mechanisms are still scarce. Therefore, the aim of the present study was to investigate a serine protease component of Nemopilema nomurai jellyfish venom (NnV) and unveil its characteristics. METHODS: To determine the relationship between fibrinolytic activity of NnV and the serine protease, fibrin zymography was performed using metalloprotease and serine protease inhibitors...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28814639/deposition-and-hydrolysis-of-serine-dipeptide-lipids-of-bacteroidetes-bacteria-in-human-arteries-relationship-to-atherosclerosis
#11
Reza Nemati, Christopher Dietz, Emily J Anstadt, Jorge Cervantes, Yaling Liu, Floyd E Dewhirst, Robert B Clark, Sydney Finegold, James J Gallagher, Michael B Smith, Xudong Yao, Frank C Nichols
Multiple reaction monitoring mass spectrometry (MRM-MS) analysis of lipid extracts from human carotid endarterectomy and carotid artery samples from young individuals consistently demonstrated the presence of bacterial serine dipeptide lipid classes including Lipid 654, an agonist for human and mouse Toll-like receptor 2, and Lipid 430, the deacylated product of Lipid 654. The relative levels of Lipid 654 and Lipid 430 were also determined in common oral and intestinal bacteria from the phylum Bacteroidetes, and human serum and brain samples from healthy adults...
August 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28814511/targeting-phospholipase-d4-attenuates-kidney-fibrosis
#12
Priyanka Trivedi, Ramya K Kumar, Ashwin Iyer, Sarah Boswell, Casimiro Gerarduzzi, Vivekkumar P Dadhania, Zach Herbert, Nikita Joshi, James P Luyendyk, Benjamin D Humphreys, Vishal S Vaidya
Phospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury...
August 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28814267/sex-and-tissue-specific-gene-expression-patterns-identified-following-de-novo-transcriptomic-analysis-of-the-norway-lobster-nephrops-norvegicus
#13
Guiomar Rotllant, Tuan Viet Nguyen, Valerio Sbragaglia, Lifat Rahi, Kevin J Dudley, David Hurwood, Tomer Ventura, Joan B Company, Vincent Chand, Jacopo Aguzzi, Peter B Mather
BACKGROUND: The Norway lobster, Nephrops norvegicus, is economically important in European fisheries and is a key organism in local marine ecosystems. Despite multi-faceted scientific interest in this species, our current knowledge of genetic resources in this species remains very limited. Here, we generated a reference de novo transcriptome for N. norvegicus from multiple tissues in both sexes. Bioinformatic analyses were conducted to detect transcripts that were expressed exclusively in either males or females...
August 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28813526/mtor-has-a-developmental-stage-specific-role-in-mitochondrial-fitness-independent-of-conventional-mtorc1-and-mtorc2-and-the-kinase-activity
#14
Khalid W Kalim, Shuangmin Zhang, Xiaoyi Chen, Yuan Li, Jun-Qi Yang, Yi Zheng, Fukun Guo
The mammalian target of rapamycin (mTOR), present in mTOR complex 1 (mTORC1) and mTORC2, is a serine/threonine kinase that integrates nutrients, growth factors, and cellular energy status to control protein synthesis, cell growth, survival and metabolism. However, it remains elusive whether mTOR plays a developmental stage-specific role in tissue development and whether mTOR can function independent of its complexes and kinase activity. In this study, by inducible genetic manipulation approach, we investigated the role of mTOR and its dependence on mTOR complexes and kinase activity in mitochondrial fitness of early, progenitor stage (lineage-negative; Lin-) versus later, lineage-committed stage (lineage-positive; Lin+) of hematopoietic cells...
2017: PloS One
https://www.readbyqxmd.com/read/28813487/effect-of-masticatory-stimulation-on-the-quantity-and-quality-of-saliva-and-the-salivary-metabolomic-profile
#15
Nobuyuki Okuma, Makiko Saita, Noriyuki Hoshi, Tomoyoshi Soga, Masaru Tomita, Masahiro Sugimoto, Katsuhiko Kimoto
BACKGROUND: This study characterized the changes in quality and quantity of saliva, and changes in the salivary metabolomic profile, to understand the effects of masticatory stimulation. METHODS: Stimulated and unstimulated saliva samples were collected from 55 subjects and salivary hydrophilic metabolites were comprehensively quantified using capillary electrophoresis-time-of-flight mass spectrometry. RESULTS: In total, 137 metabolites were identified and quantified...
2017: PloS One
https://www.readbyqxmd.com/read/28813411/mammals-divert-endogenous-genotoxic-formaldehyde-into-one-carbon-metabolism
#16
Guillermo Burgos-Barragan, Niek Wit, Johannes Meiser, Felix A Dingler, Matthias Pietzke, Lee Mulderrig, Lucas B Pontel, Ivan V Rosado, Thomas F Brewer, Rebecca L Cordell, Paul S Monks, Christopher J Chang, Alexei Vazquez, Ketan J Patel
The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#17
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28811476/lyn-and-fyn-function-as-molecular-switches-that-control-immunoreceptors-to-direct-homeostasis-or-inflammation
#18
Sanae Ben Mkaddem, Amaya Murua, Héloise Flament, Dimitri Titeca-Beauport, Carine Bounaix, Luca Danelli, Pierre Launay, Marc Benhamou, Ulrich Blank, Eric Daugas, Nicolas Charles, Renato C Monteiro
Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28811266/expression-and-purification-of-a-difficult-sarcomeric-protein-telethonin
#19
Huanbo Tan, Wencheng Su, Pengju Wang, Wenyu Zhang, Michael Sattler, Peijian Zou
Telethonin anchors the N-terminal region of titin in the Z-disk of the sarcomere by binding to two immunoglobulin-like (Ig) domains (Z1 and Z2) of titin (Z1Z2). Thereby telethonin plays an important role in myofibril assembly and in muscle development and functional regulation. The expression and purification of recombinant telethonin is very challenging. In previous studies, recombinant telethonin expressed from E. coli was refolded in the presence of Z1Z2. Here, we report various strategies to establish a reliable and efficient protocol for the preparation of telethonin and titin Z1Z2 protein...
August 12, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28810924/mutational-analysis-of-col1a1-and-col1a2-genes-among-estonian-osteogenesis-imperfecta-patients
#20
Lidiia Zhytnik, Katre Maasalu, Ene Reimann, Ele Prans, Sulev Kõks, Aare Märtson
BACKGROUND: Osteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identify the mutational spectrum of COL1A1/2 genes in Estonian patients. The small population size of Estonia provides a unique chance to explore the collagen I mutational profile of 100% of OI families in the country. METHODS: We performed mutational analysis of peripheral blood gDNA of 30 unrelated Estonian OI patients using Sanger sequencing of COL1A1 and COL1A2 genes, including all intron-exon junctions and 5'UTR and 3'UTR regions, to identify causative OI mutations...
August 15, 2017: Human Genomics
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