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https://www.readbyqxmd.com/read/29786498/hcov-229e-spike-protein-fusion-activation-by-trypsin-like-serine-proteases-is-mediated-by-proteolytic-processing-in-the-s2-region
#1
Ariane Bonnin, Adeline Danneels, Jean Dubuisson, Anne Goffard, Sandrine Belouzard
Human coronavirus 229E (HCoV-229E) is responsible for common colds. Like other coronaviruses, HCoV-229E exploits cellular proteases to activate fusion mediated by the spike protein. We analysed the proteolytic processing of the HCoV-229E spike protein by trypsin-like serine proteases leading to activation of the fusion process. Unlike in other coronaviruses, HCoV-229E fusion activation appears to be a one-step process. Indeed, cleavage of the S1/S2 interface does not seem to be a prerequisite, and the fusion activation is highly reliant on the S2' region, with arginine residue 683 acting as the recognition site...
May 22, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29786422/mechanisms-regulating-the-association-of-protein-phosphatase-1-with-spinophilin-and-neurabin
#2
Michael C Edler, Asma B Salek, Darryl S Watkins, Harjot Kaur, Cameron W Morris, Bryan K Yamamoto, Anthony J Baucum
Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homolog neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins...
May 22, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29785949/-the-functions-of-yhcz-gene-during-bacillus-thuringiensis-growth
#3
Lin da Jia, Tan Tan Gao, Qi Peng, Jing Lv, Jie Zhang, Min Chen, Fu Ping Song
yhcZ and yhcY genes constitute a two-component system in Bacillus subtilis and B. cereus that regulates bacterial growth. However, the exact biological function of yhcZ gene in B. thuringiensis has not been fully elucidated. In this study, we proved that HD73_5824 is an yhcZ gene in B. thuringiensis subsp. kurstaki HD73 strain by combining gene functional annotation, analysis of upstream and downstream genes arrangement, and amino acid sequence alignment. This yhcZ gene may co-regulate bacterial growth with HD73_5825 gene (yhcY gene) by constituting a two-component system...
May 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29785722/electrostatic-recognition-in-substrate-binding-to-serine-proteases
#4
Birgit J Waldner, Johannes Kraml, Ursula Kahler, Alexander Spinn, Michael Schauperl, Maren Podewitz, Julian E Fuchs, Gabriele Cruciani, Klaus R Liedl
Serine proteases of the Chymotrypsin family are structurally very similar but have very different substrate preferences. This study investigates a set of 9 different proteases of this family comprising proteases that prefer substrates containing positively charged amino acids, negatively charged amino acids, and uncharged amino acids with varying degree of specificity. Here, we show that differences in electrostatic substrate preferences can be predicted reliably by electrostatic molecular interaction fields employing customized GRID probes...
May 22, 2018: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29785573/effect-of-dietary-soy-oil-glucose-and-glutamine-on-growth-performance-amino-acid-profile-blood-profile-immunity-and-antioxidant-capacity-in-weaned-piglets
#5
Dinghong Lv, Xia Xiong, Huansheng Yang, Meiwei Wang, Yijie He, Yanhong Liu, Yulong Yin
Weaning stress results in gastrointestinal dysfunction and depressed performance in pigs. This study aimed to investigate the effect of soy oil, glucose, and glutamine on the growth and health of weaned piglets. Compared with those in the glutamine group, piglets in the glucose and soy oil groups had greater average daily gain, average daily feed intake, and gain: feed ratio from day 0 to 14, and gain: feed ratio for the overall period. There were no differences with regard to serum amino acids among the three groups on day 14, except glycine and threonine...
May 18, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29785432/molecular-insights-into-avibactam-mediated-class-c-%C3%AE-lactamase-inhibition-competition-between-reverse-acylation-and-hydrolysis-through-desulfation
#6
Chandan Kumar Das, Nisanth N Nair
Avibactam is one of the promising next generation β-lactamase inhibitors due to its exceptional inhibition against wide-spectrum serine β-lactamases. The unusual reversible acylation mechanism has particularly gained interest to explain the inhibition mechanism of avibactam. We explore the mechanism of acylation and deacylation involving avibactam in class-C β-lactamases (CBLs) through hybrid quantum mechanical/molecular mechanical (QM/MM) enhanced sampling molecular dynamics (MD) simulations. Based on these computations, we probe the kinetic stability of the acyl-enzyme complex formed by avibactam and CBLs, thereby gaining molecular level insights into the avibactam-mediated inhibition of CBLs...
May 22, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29785216/-staphylococcus-aureus-surface-protein-g-is-an-immunodominant-protein-and-a-possible-target-in-an-anti-biofilm-drug-development
#7
Yury Belyi, Ivan Rybolovlev, Nikita Polyakov, Alena Chernikova, Irina Tabakova, Alexandre Gintsburg
Background: Staphylococcus aureus is a Gram-positive bacterium that causes severe illnesses in the human population. The capacity of S. aureus strains to form biofilms on biotic and abiotic surfaces creates serious problems for treatment of hospital infections and has stimulated efforts to develop new means of specific protection or immunotherapy. Material and Methods: We found that rabbit serum raised against crude concentrated S. aureus liquid culture significantly decreased the development of staphylococcal biofilm in vitro ...
2018: Open Microbiology Journal
https://www.readbyqxmd.com/read/29784830/structural-basis-of-o-glcnac-recognition-by-mammalian-14-3-3-proteins
#8
Clifford A Toleman, Maria A Schumacher, Seok-Ho Yu, Wenjie Zeng, Nathan J Cox, Timothy J Smith, Erik J Soderblom, Amberlyn M Wands, Jennifer J Kohler, Michael Boyce
O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events remain uncharacterized. One prevalent hypothesis is that O-GlcNAc moieties may be recognized by "reader" proteins to effect downstream signaling. However, no general O-GlcNAc readers have been identified, leaving a considerable gap in the field. To elucidate O-GlcNAc signaling mechanisms, we devised a biochemical screen for candidate O-GlcNAc reader proteins...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784816/encephalitis-is-mediated-by-rop18-of-toxoplasma-gondii-a-severe-pathogen-in-aids-patients
#9
Ran An, Yuewen Tang, Lijian Chen, Haijian Cai, De-Hua Lai, Kang Liu, Lijuan Wan, Linli Gong, Li Yu, Qingli Luo, Jilong Shen, Zhao-Rong Lun, Francisco J Ayala, Jian Du
The neurotropic parasite Toxoplasma gondii is a globally distributed parasitic protozoan among mammalian hosts, including humans. During the course of infection, the CNS is the most commonly damaged organ among invaded tissues. The polymorphic rhoptry protein 18 (ROP18) is a key serine (Ser)/threonine (Thr) kinase that phosphorylates host proteins to modulate acute virulence. However, the basis of neurotropism and the specific substrates through which ROP18 exerts neuropathogenesis remain unknown. Using mass spectrometry, we performed proteomic analysis of proteins that selectively bind to active ROP18 and identified RTN1-C, an endoplasmic reticulum (ER) protein that is preferentially expressed in the CNS...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784539/revisiting-antithrombin-in-health-and-disease-congenital-deficiencies-and-genetic-variants-and-laboratory-studies-on-%C3%AE-and-%C3%AE-forms
#10
REVIEW
Jean Amiral, Jerard Seghatchian
Antithrombin [AT] is the main inhibitor for activated plasma coagulation serine esterases, inhibiting thrombin, Factors Xa and IXa, but also Factors XIIa, XIa, VIIa, kallicrein, and plasmin. Its activity is highly enhanced by heparin, through binding to the pentasaccharide sequences, for inhibition of all coagulation proteases, except thrombin, which inhibition requires its additional binding to the heparin polysaccharide chain. However, AT is the major inhibitor of thrombin in the blood circulation. Congenital or acquired deficiencies of AT expose affected patients to an increased risk of developing unprovoked and recurrent thrombo-embolic diseases...
April 19, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29783958/sanguinarine-triggers-intrinsic-apoptosis-to-suppress-colorectal-cancer-growth-through-disassociation-between-strap-and-melk
#11
Xianling Gong, Zhihong Chen, Qinrui Han, Chunhui Chen, Linlin Jing, Yawei Liu, Liang Zhao, Xueqing Yao, Xuegang Sun
BACKGROUND: Previous studies showed sanguinarine induced apoptosis in CRC cells but did not define the underlying mechanisms. The purpose of this work was to determine the in vivo and in vitro effects of sanguinarine on CRC tumors and to elucidate the mechanism in regulating the intrinsic apoptosis. METHODS: Cell viability of CRC cell lines treated with sanguinarine was measured by MTT assay. Apoptotic cells stained with Annexin V and 7-AAD were detected by flow cytometry...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29783741/serine-protease-inhibitor-serpine2-reversibly-modulates-murine-sperm-capacitation
#12
Sheng-Hsiang Li, Yuh-Ming Hwu, Chung-Hao Lu, Ming-Huei Lin, Ling-Yu Yeh, Robert Kuo-Kuang Lee
SERPINE2 (serpin peptidase inhibitor, clade E, member 2), predominantly expressed in the seminal vesicle, can inhibit murine sperm capacitation, suggesting its role as a sperm decapacitation factor (DF). A characteristic of DF is its ability to reverse the capacitation process. Here, we investigated whether SERPINE2 can reversibly modulate sperm capacitation. Immunocytochemical staining revealed that SERPINE2 was bound onto both capacitated and uncapacitated sperm. It reversed the increase in BSA-induced sperm protein tyrosine phosphorylation levels...
May 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29782854/combined-treatment-with-sorafenib-and-silibinin-synergistically-targets-both-hcc-cells-and-cancer-stem-cells-by-enhanced-inhibition-of-the-phosphorylation-of-stat3-erk-akt
#13
Jie Mao, Hongbao Yang, Tingting Cui, Pan Pan, Nadia Kabir, Duo Chen, Jinyan Ma, Xingyi Chen, Yijun Chen, Yong Yang
Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782227/cdk5-mediated-acn-acinus-phosphorylation-regulates-basal-autophagy-independently-of-metabolic-stress
#14
Nilay Nandi, Helmut Krämer
In neurons, autophagy counteracts consequences of aging. It is therefore of interest how basal rates of macroautophagy/autophagy can be controlled independently of metabolic stress. We recently investigated the regulation of basal, starvation-independent autophagy by Acn/Acinus, a multifunctional nuclear protein with proposed roles in apoptosis, alternative RNA splicing, and basal autophagy. We found that Acn is stabilized by phosphorylation of the conserved serine 437. The phosphomimetic AcnS437D mutation causes no overt developmental phenotypes, but significantly elevates levels of basal autophagy and extends life spans...
May 21, 2018: Autophagy
https://www.readbyqxmd.com/read/29782177/synthesis-of-%C3%AE-%C3%AE-difluorinated-phosphonate-pser-pthr-mimetics-via-rhodium-catalyzed-asymmetric-hydrogenation-of-%C3%AE-difluorophosphonomethyl-%C3%AE-acylamino-acrylates
#15
Hong-Xue Chen, Jie Kang, Rong Chang, Yun-Lai Zhang, Hua-Zhen Duan, Yan-Mei Li, Yong-Xiang Chen
A novel and facile synthetic strategy for α,α-difluorinated phosphonate mimetics of phosphoserine/phosphothreonine utilizing rhodium-catalyzed asymmetric hydrogenation was developed. The dehydrogenated substrate β-difluorophosphonomethyl α-(acylamino)acrylates were first prepared from protected serine/threonine followed by asymmetric hydrogenation using the rhodium-DuPhos catalytic system to generate the chiral center(s). These important phosphonate building blocks were successfully incorporated into phosphatase-resistant peptides, which displayed similar inhibition to the 14-3-3 ζ protein as the parent pSer/pThr peptides...
May 21, 2018: Organic Letters
https://www.readbyqxmd.com/read/29782000/induction-of-nephrotic-syndrome-in-mice-by-retrobulbar-injection-of-doxorubicin-and-prevention-of-volume-retention-by-sustained-release-aprotinin
#16
Bernhard N Bohnert, Ferruh Artunc
Nephrotic syndrome is the most extreme manifestation of proteinuric kidney disease and characterized by heavy proteinuria, hypoalbuminemia, and edema due to sodium retention and hyperlipidemia. To study the pathophysiology of this syndrome, rodent models have been developed based on the injection of toxic substances such as doxorubicin causing podocyte damage. In mice, only few strains are susceptible to this model. In wildtype 129S1/SvImJ mice, the administration of doxorubicin by rapid intravenous injection to the retrobulbar sinus induces experimental nephrotic syndrome that features all the symptoms of human disease including sodium retention and edema...
May 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781215/strap-deficiency-impairs-mouse-embryonic-stem-cells-lineage-commitment-through-cyp26a1-mediated-retinoic-acid-homeostasis
#17
Lin Jin, Chenbei Chang, Kevin M Pawlik, Arunima Datta, Larry M Johnson, Trung Vu, Joseph L Napoli, Pran K Datta
Retinoic acid (RA) signaling is essential for the differentiation of embryonic stem cells (ESCs) and vertebrate development. RA biosynthesis and metabolism are controlled by a series of enzymes, but the molecular regulators of these enzymes remain largely obscure. In this study, we investigated the functional role of the WD-domain protein STRAP (serine threonine kinase receptor-associated protein) in the pluripotency and lineage commitment of murine ESCs. We generated Strap knockout (KO) mouse ESCs and subjected them to spontaneous differentiation...
May 21, 2018: Stem Cells
https://www.readbyqxmd.com/read/29781146/modulation-of-serine-threonine-phosphatases-by-melatonin-therapeutic-approaches-in-neurodegenerative-diseases
#18
REVIEW
Raquel L Arribas, Alejandro Romero, Javier Egea, Cristóbal de Los Ríos
Melatonin is an endogenous hormone produced by the pineal gland as well as many other tissues and organs. The natural decline in melatonin levels with aging strongly contributes to the development of neurodegenerative disorders. Neurodegenerative diseases share common mechanisms of toxicity such as proteinopathy, mitochondrial dysfunction, metal dyshomeostasis, oxidative stress, neuroinflammation, and an imbalance in the phosphorylation/dephosphorylation ratio. Several reports have proved the usefulness of melatonin in counteracting the events that lead to a neurodegenerative scenario...
May 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29780501/a-bi-terminal-protein-ligation-strategy-to-probe-chromatin-structure-during-dna-damage
#19
Sinan Kilic, Iuliia Boichenko, Carolin C Lechner, Beat Fierz
The cellular response to DNA damage results in a signaling cascade that primes chromatin for repair. Combinatorial post-translational modifications (PTMs) play an important role in this process by altering the physical properties of chromatin and recruiting downstream factors. One key signal integrator is the histone variant H2A.X, which is phosphorylated at a C-terminal serine (S139ph), and ubiquitylated within its N-terminal tail at lysines 13 and 15 (K13/15ub). How these PTMs directly impact chromatin structure and thereby facilitate DNA repair is not well understood...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29779956/targeted-covalent-inhibition-of-prolyl-oligopeptidase-pop-discovery-of-sulfonylfluoride-peptidomimetics
#20
Salvador Guardiola, Roger Prades, Laura Mendieta, Arwin J Brouwer, Jelle Streefkerk, Laura Nevola, Teresa Tarragó, Rob M J Liskamp, Ernest Giralt
Prolyl oligopeptidase (POP), a serine protease highly expressed in the brain, has recently emerged as an enticing therapeutic target for the treatment of cognitive and neurodegenerative disorders. However, most reported inhibitors suffer from short duration of action, poor protease selectivity, and low blood-brain barrier (BBB) permeability, which altogether limit their potential as drugs. Here, we describe the structure-based design of the first irreversible, selective, and brain-permeable POP inhibitors. At low-nanomolar concentrations, these covalent peptidomimetics produce a fast, specific, and sustained inactivation of POP, both in vitro and in human cells...
May 7, 2018: Cell Chemical Biology
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