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serin protease inhibitor

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https://www.readbyqxmd.com/read/29142062/the-serine-protease-inhibitor-neuroserpin-is-required-for-normal-synaptic-plasticity-and-regulates-learning-and-social-behavior
#1
Rebecca Reumann, Ricardo Vierk, Lepu Zhou, Frederice Gries, Vanessa Kraus, Julia Mienert, Eva Romswinkel, Fabio Morellini, Isidre Ferrer, Chiara Nicolini, Margaret Fahnestock, Gabriele Rune, Markus Glatzel, Giovanna Galliciotti
The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the adult brain. The physiological expression pattern of neuroserpin, its high degree of colocalization with tPA within the CNS, together with its dysregulation in neuropsychiatric disorders, suggest a role in formation and refinement of synapses...
December 2017: Learning & Memory
https://www.readbyqxmd.com/read/29133118/functional-characterization-of-a-serine-protease-inhibitor-modulated-in-the-infection-of-the-aedes-aegypti-with-dengue-virus
#2
Tatiane Sanches Soares, Boris Luis Rodriguez Gonzalez, Ricardo José Soares Torquato, Francisco Jose Alves Lemos, André L Costa-da-Silva, Margareth de Lara Capurro Guimarães, Aparecida Sadae Tanaka
During feeding with blood meal, female Aedes aegypti can transmit infectious agents, such as dengue, yellow fever, chikungunya and Zika viruses. Dengue virus causes human mortality in tropical regions of the world, and there is no specific treatment or vaccine with maximum efficiency being used for these infections. In the vector-virus interaction, the production of several molecules is modulated by both mosquitoes and invading agents. However, little information is available about these molecules in the Ae...
November 10, 2017: Biochimie
https://www.readbyqxmd.com/read/29132840/d-peptides-as-inhibitors-of-pr3-membrane-interactions
#3
Ksenia Maximova, Tom Venken, Nathalie Reuter, Joanna Trylska
Proteinase 3 (PR3) is a neutrophil serine protease present in cytoplasmic granules but also expressed at the neutrophil surface where it mediates proinflammatory effects. Studies of the underlying molecular mechanisms have been hampered by the lack of inhibitors of the PR3 membrane anchorage. Indeed while there exist inhibitors of the catalytic activity of PR3, its membrane interfacial binding site (IBS) is distinct from its catalytic site. The IBS has been characterized both by mutagenesis experiments and molecular modeling...
November 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29129633/sequence-and-structure-insights-of-kazal-type-thrombin-inhibitor-protein-studied-with-phylogeny-homology-modeling-and-dynamic-mm-gbsa-studies
#4
Aparna Jadhav, RadhaCharan Dash, Raj Hirwani, Malik Abdin
Despite the wide medical importance of serine protease inhibitors, many of kazal type proteins are still to be explored. These thrombin inhibiting proteins are found in the digestive system of hematophagous organisms mainly Arthropods. We studied one of such protein i.e. Kazal type-1 protein from sand-fly Phlebotomus papatasi as its structure and interaction with thrombin is unclear. Initially, Dipetalin a kazal-follistasin domain protein was run through PSI-BLAST to retrieve related sequences. Using this set of sequence a phylogenetic tree was constructed, which identified a distantly related kazal type-1 protein...
November 9, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29127014/structural-insights-and-binding-of-a-natural-ligand-succinic-acid-with-serine-and-cysteine-proteases
#5
R Manohar, N H V Kutumbarao, Raghavendra Sashi Krishna Nagampalli, D Velmurugan, K Gunasekaran
In the age of growing infectious diseases, there is a great demand for new inhibitors which can exhibit minimum side effects. Owing to the importance of proteases in life cycle and invasion, they have been projected as attractive targets for structure based drug designing against microbes including viruses. Here we report the inhibitory activity of a well known natural compound succinic acid against both serine and cysteine proteases. The ligand is found co-crystallized with Bovine pancreatic trypsin in one of our crystallization trials and the diffraction data up to1...
November 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29126758/maspin-expression-and-subcellular-localization-in-invasive-ductal-carcinoma-of-the-breast-prognostic-significance-and-relation-to-microvessel-density
#6
Duaa S Helal, Dina M El-Guindy
Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor...
November 7, 2017: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/29118397/the-kunitz-domain-i-of-hepatocyte-growth-factor-activator-inhibitor-2-inhibits-matriptase-activity-and-invasive-ability-of-human-prostate-cancer-cells
#7
Shang-Ru Wu, Chen-Hsin Teng, Ya-Ting Tu, Chun-Jung Ko, Tai-Shan Cheng, Shao-Wei Lan, Hsin-Ying Lin, Hsin-Hsien Lin, Hsin-Fang Tu, Pei-Wen Hsiao, Hsiang-Po Huang, Chung-Hsin Chen, Ming-Shyue Lee
Dysregulation of pericellular proteolysis is often required for tumor invasion and cancer progression. It has been shown that down-regulation of hepatocyte growth factor activator inhibitor-2 (HAI-2) results in activation of matriptase (a membrane-anchored serine protease), human prostate cancer cell motility and tumor growth. In this study, we further characterized if HAI-2 was a cognate inhibitor for matriptase and identified which Kunitz domain of HAI-2 was required for inhibiting matriptase and human prostate cancer cell motility...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115822/single-quantum-dot-based-nanosensor-for-sensitive-detection-of-o-glcnac-transferase-activity
#8
Juan Hu, Yueying Li, Ying Li, Bo Tang, Chun-Yang Zhang
Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes and neurodegenerative disease. Here, we develop a single quantum dot (QD)-based nanosensor for sensitive OGT assay. We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate...
November 8, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29114958/evidence-for-multiple-modes-of-neutrophil-serine-protease-recognition-by-the-eap-family-of-staphylococcal-innate-immune-evasion-proteins
#9
Daphne A C Stapels, Jordan L Woehl, Fin J Milder, Angelino T Tromp, Aernoud A van Batenburg, Wilco C de Graaf, Samuel C Broll, Natalie M White, Suzan H M Rooijakkers, Brian V Geisbrecht
Neutrophils contain high levels of chymotrypsin-like serine proteases (NSPs) within their azurophilic granules that have a multitude of functions within the immune system. In response, the pathogen Staphylococcus aureus has evolved three potent inhibitors (Eap, EapH1, and EapH2) that protect the bacterium as well as several of its secreted virulence factors from the degradative action of NSPs. We previously showed that these so-called EAP domain proteins represent a novel class of NSP inhibitors characterized by a non-covalent inhibitory mechanism and a distinct target specificity profile...
November 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29107700/general-and-modular-strategy-for-designing-potent-selective-and-pharmacologically-compliant-inhibitors-of-rhomboid-proteases
#10
Anežka Tichá, Stancho Stanchev, Kutti R Vinothkumar, David C Mikles, Petr Pachl, Jakub Began, Jan Škerle, Kateřina Švehlová, Minh T N Nguyen, Steven H L Verhelst, Darren C Johnson, Daniel A Bachovchin, Martin Lepšík, Pavel Majer, Kvido Strisovsky
Rhomboid-family intramembrane proteases regulate important biological processes and have been associated with malaria, cancer, and Parkinson's disease. However, due to the lack of potent, selective, and pharmacologically compliant inhibitors, the wide therapeutic potential of rhomboids is currently untapped. Here, we bridge this gap by discovering that peptidyl α-ketoamides substituted at the ketoamide nitrogen by hydrophobic groups are potent rhomboid inhibitors active in the nanomolar range, surpassing the currently used rhomboid inhibitors by up to three orders of magnitude...
October 12, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29107082/purification-and-characterization-of-an-anti-hemorrhagic-protein-from-naja-naja-indian-cobra-venom
#11
K N Suvilesh, M Yariswamy, M N Savitha, Vikram Joshi, A N Nanjaraj Urs, Amog P Urs, M Choudhury, D Velmurugan, B S Vishwanath
Snake venom Kunitz-type proteins are well known to inhibit serine proteases but a few studies have also shown matrix metalloproteases (MMPs) inhibition. In view of the fact that MMPs and snake venom metalloproteases (SVMPs) have similar catalytic site, inhibition of SVMP activity by Kunitz-type proteins remains to be studied. Recent proteomic studies of Naja naja (N. naja) venom revealed the abundance of Kunitz-type proteins. In this regard, present study aimed at purification of a protease inhibitor from N...
October 26, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29106998/anti-apoptotic-serine-protease-inhibitors-contribute-towards-the-survival-of-allergenic-th2-cells
#12
Mohamed H Shamji, Jeff N Temblay, Wei Cheng, Susan M Byrne, Ellen Macfarlane, Amy R Switzer, Natalia D C Francisco, Fedina Olexandra, Fabian Jacubczik, Stephen R Durham, Philip G Ashton-Rickardt
BACKGROUND: The mechanisms regulating the maintenance of persistent Th2 cells that potentiate allergic inflammation are not well understood. OBJECTIVE: The function of Serine Protease Inhibitor 2A (Spi2A) was studied in mouse Th2 cells and Serine Protease Inhibitor (SERPIN) B3 and B4 genes were studied in Th2 cells from grass pollen allergic individuals. METHODS: Spi2A deficient Th2 cells were studied in vitro culture or in vivo after challenge of Spi2A Knock-Out (KO) mice with ovalbumin in alum...
October 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29105834/characterization-of-a-robust-serine-protease-from-bacillus-subtilis-k-1
#13
Satbir Singh, Puneet Gupta, Bijender K Bajaj
Process apt microbial proteases due to their wide range industrial applications have become the focus of intense scientific research during recent years. Considering the hostile process milieu, the proteases intended for application must be robust enough to withstand the extremes of temperature and pH, and presence of organic solvents and other potential enzyme inhibitors. Current study presents the characterization of a robust protease from a previously isolated bacterium Bacillus subtilis K-1 (BSK-1). Purification of BSK-1 protease (5...
November 6, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29104489/structural-principles-in-the-development-of-cyclic-peptidic-enzyme-inhibitors
#14
REVIEW
Peng Xu, Peter A Andreasen, Mingdong Huang
This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29100036/nafamostat-mesilate-a-serine-protease-inhibitor-suppresses-interferon-gamma-induced-up-regulation-of-programmed-cell-death-ligand-1-in-human-cancer-cells
#15
Sadamu Homma, Kazumi Hayashi, Kosaku Yoshida, Yukiko Sagawa, Yuko Kamata, Masaki Ito
Programmed cell death ligand-1 (PD-L1) plays a pivotal role in the suppression of antitumour immunity by binding to programmed cell death-1 (PD-1) on tumouricidal cytotoxic T lymphocytes (CTLs), rendering them inactive. As blockade of PD-1/PD-L1 interaction by the monoclonal antibodies induced effective T cell-mediated antitumour response, suppression of PD-L1 expression in tumour cells by the chemical agent might contribute to treatment against malignant tumours. Nafamostat mesilate (NM), a serine protease inhibitor that is frequently used in the clinic, potently suppressed interferon-gamma (IFN-gamma)-induced up-regulation of PD-L1 in cultured human lung cancer cells (HLC-1) at both the messenger RNA (mRNA) and protein levels...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29096562/alpha-1-antitrypsin-ameliorates-ventilator-induced-lung-injury-in-rats-by-inhibiting-inflammatory-responses-and-apoptosis
#16
He Zhu, Jianshuai He, Jia Liu, Xin Zhang, Fengyun Yang, Pingting Liu, Shilei Wang
Mechanical ventilation is extensively used to treat patients with lung injury but may result in ventilator-induced lung injury (VILI). The present study investigated the protective effect of alpha 1-antitrypsin (AAT) on VILI. Adult male rats were subjected to sham, ventilation + saline, or ventilation + AAT treatment and lung injuries were evaluated. Peripheral blood and bronchoalveolar lavage fluid (BALF) were obtained to assess systemic and local inflammatory responses, respectively. Mechanical ventilation resulted in lung injury, as evidenced by histological abnormalities as well as elevations in PaO2/FiO2 ratio, the wet-to-dry weight ratio, and the BALF level of proteins...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29093471/antithrombotic-properties-of-jj1-a-potent-and-novel-thrombin-inhibitor
#17
Wonhwa Lee, Suyeon Lee, Joonhyeok Choi, Jun-Hyeong Park, Kyung-Min Kim, Jun-Goo Jee, Jong-Sup Bae
The development of new anticoagulants is an important goal for the improvement of thrombosis treatment. Recent studies have suggested the importance of thrombin inhibitors in the modulation of thromboembolic disorders. The aim of this study was to discover a new small-molecule thrombin inhibitor. In this study, the compound JJ1, which has a novel scaffold, was selected by structure-based docking simulation to determine its potential inhibitory activity against thrombin. JJ1 was shown to inhibit the catalytic activity of human α-thrombin with a K i of 0...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29089436/protease-mediated-suppression-of-drg-neuron-excitability-by-commensal-bacteria
#18
Jessica L Sessenwein, Corey C Baker, Sabindra Pradhananga, Megan E Maitland, Elaine O Petrof, Emma Allen-Vercoe, Curtis Noordhof, David E Reed, Stephen J Vanner, Alan E Lomax
Peripheral pain signaling reflects a balance of pro and anti-nociceptive influences; the contribution by the gastrointestinal (GI) microbiota to this balance has received little attention. Disorders such as inflammatory bowel disease and irritable bowel syndrome are associated with exaggerated visceral nociceptive actions that may involve altered microbial signaling, particularly given the evidence for bacterial dysbiosis. Thus, we tested whether a community of commensal GI bacteria derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) can affect the excitability of male mouse dorsal root ganglion (DRG) neurons...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29084210/zeb1-repressed-micrornas-inhibit-autocrine-signaling-that-promotes-vascular-mimicry-of-breast-cancer-cells
#19
E M Langer, N D Kendsersky, C J Daniel, G M Kuziel, C Pelz, K M Murphy, M R Capecchi, R C Sears
During normal tumor growth and in response to some therapies, tumor cells experience acute or chronic deprivation of nutrients and oxygen and induce tumor vascularization. While this occurs predominately through sprouting angiogenesis, tumor cells have also been shown to directly contribute to vessel formation through vascular mimicry (VM) and/or endothelial transdifferentiation. The extrinsic and intrinsic mechanisms underlying tumor cell adoption of endothelial phenotypes, however, are not well understood...
October 30, 2017: Oncogene
https://www.readbyqxmd.com/read/29079225/digestive-enzymes-of-the-californian-two-spot-octopus-octopus-bimaculoides-pickford-and-mcconnaughey-1949
#20
Laura Elizabeth Ibarra-García, Dariel Tovar-Ramírez, Carlos Rosas, Ángel Isidro Campa-Córdova, José Manuel Mazón-Suástegui
Octopus bimaculoides is an important commercially fished species in the California Peninsula with aquaculture potential; however, to date limited information is available regarding its digestive physiology. The objective of this study was focused on biochemically characterizing the main enzymes involved in the digestion of O. bimaculoides. Optimum pH, temperature and thermostability were determined for amylases, lipases, trypsin and chymotrypsin; optimum pH and protease inhibitor effect were assessed for acidic and alkaline proteases, and the effect of divalent ions on trypsin and chymotrypsin activity was evaluated in enzymatic extracts from the digestive (DG) and salivary glands (SG) and crop gastric juices (GJ)...
October 24, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
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