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serin protease inhibitor

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https://www.readbyqxmd.com/read/27905021/netherton-syndrome-a-genotype-phenotype-review
#1
REVIEW
Constantina A Sarri, Angeliki Roussaki-Schulze, Yiannis Vasilopoulos, Efterpi Zafiriou, Aikaterini Patsatsi, Costas Stamatis, Polyxeni Gidarokosta, Dimitrios Sotiriadis, Theologia Sarafidou, Zissis Mamuris
Netherton syndrome (OMIM #256500) is a rare but severe autosomal recessive form of ichthyosis that affects the skin, hair, and immune system. The identification of SPINK5, which encodes for the serine protease inhibitor LEKTI, as the gene responsible for Netherton syndrome, enabled the search for causative mutations in Netherton syndrome patients and families. However, information regarding these mutations and their association with the pathological Netherton syndrome phenotype is scarce. Herein, we provide an up-to-date overview of 80 different mutations in exonic as well as intronic regions that have been currently identified in 172 homozygous or compound heterozygous patients from 144 families...
November 30, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27903800/genetic-variability-of-myxoma-virus-genomes
#2
Christoph Braun, Andrea Thürmer, Rolf Daniel, Anne-Kathrin Schultz, Ingo Bulla, Horst Schirrmeier, Dietmar Mayer, Andreas Neubert, Claus-Peter Czerny
: Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 Myxoma virus strains (MYXV) were sequenced: German field isolates Munich-1, FLI-H, 2604, 3207, vaccine strain MAV, and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207) in size...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27899813/the-pro-fibrotic-role-of-dipeptidyl-peptidase-4-in-carbon-tetrachloride-induced-experimental-liver-injury
#3
Xin M Wang, Lauren E Holz, Sumaiya Chowdhury, Shaun P Cordoba, Kathryn A Evans, Margaret G Gall, Ana Júlia Vieira de Ribeiro, Yuan Zhou Zheng, Miriam T Levy, Denise M T Yu, Tsun-Wen Yao, Natasa Polak, Christopher J Jolly, Patrick Bertolino, Geoffrey W McCaughan, Mark D Gorrell
Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl4) in DPP4 gene knockout (gko) mice...
November 30, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27894344/siropins-novel-serine-protease-inhibitors-from-gut-microbiota-acting-on-human-proteases-involved-in-inflammatory-bowel-diseases
#4
Héla Mkaouar, Nizar Akermi, Vincent Mariaule, Samira Boudebbouze, Nadia Gaci, Florette Szukala, Nicolas Pons, Josan Marquez, Ali Gargouri, Emmanuelle Maguin, Moez Rhimi
BACKGROUND: In eukaryotes, the serpins constitute a wide family of protease inhibitors regulating many physiological pathways. Many reports stressed the key role of serpins in several human physiopathologies including mainly the inflammatory bowel diseases. In this context, eukaryotic serpins were largely studied and their use to limit inflammation was reported. In comparison to that, bacterial serpins and mainly those from human gut microbiota remain poorly studied. RESULTS: The two genes encoding for putative serpins from the human gut bacterium Eubacterium sireaum, display low sequence identities...
November 29, 2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27893815/an-accessory-protease-inhibitor-to-increase-the-yield-and-quality-of-a-tumour-targeting-mab-in-nicotiana-benthamiana-leaves
#5
Philippe V Jutras, Carla Marusic, Chiara Lonoce, Carole Deflers, Marie-Claire Goulet, Eugenio Benvenuto, Dominique Michaud, Marcello Donini
The overall quality of recombinant IgG antibodies in plants is dramatically compromised by host endogenous proteases. Different approaches have been developed to reduce the impact of endogenous proteolysis on IgGs, notably involving site-directed mutagenesis to eliminate protease-susceptible sites or the in situ mitigation of host protease activities to minimize antibody processing in the cell secretory pathway. We here characterized the degradation profile of H10, a human tumour-targeting monoclonal IgG, in leaves of Nicotiana benthamiana also expressing the human serine protease inhibitor α1-antichymotrypsin or the cysteine protease inhibitor tomato cystatin SlCYS8...
2016: PloS One
https://www.readbyqxmd.com/read/27888761/tissue-thrombin-is-associated-with-the-pathogenesis-of-dilated-cardiomyopathy
#6
Keiichi Ito, Kenichi Hongo, Taro Date, Masahiro Ikegami, Hiroshi Hano, Mamiko Owada, Satoshi Morimoto, Yusuke Kashiwagi, Daisuke Katoh, Takuya Yoshino, Akira Yoshii, Haruka Kimura, Tomohisa Nagoshi, Ichige Kajimura, Yoichiro Kusakari, Toru Akaike, Susumu Minamisawa, Kazuo Ogawa, Kosuke Minai, Takayuki Ogawa, Makoto Kawai, Junji Yajima, Seiichiro Matsuo, Teiichi Yamane, Ikuo Taniguchi, Sachio Morimoto, Michihiro Yoshimura
BACKGROUND: Thrombin is a serine protease known to be the final product of the coagulation cascade. However, thrombin plays other physiological roles in processes such as gastric contractions and vessel wound healing, and a state of coagulability is increased in patients with dilated cardiomyopathy (DCM). In this study, we investigate the role of thrombin in the pathogenesis of DCM. The purpose of this study is to clarify the role of thrombin in the pathogenesis of DCM and investigate the possibility of treatment against DCM by thrombin inhibition...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27884442/the-induction-of-the-collagen-capsule-synthesis-by-trichinella-spiralis-is-closely-related-to-protease-activated-receptor-2
#7
Mi Kyung Park, Min Kyoung Cho, Shin Ae Kang, Bo Young Kim, Hak Sun Yu
The muscle-stage larvae of the parasite Trichinella spiralis have the ability to survive within host muscle tissue by virtue of the formation a nurse cell-parasite complex, which is surrounded by collagen. The formation of the complex is initiated by excretory-secretory (ES) proteins produced by the parasite. To determine the mechanisms underlying collagen capsule formation, we investigated the expression levels of several types of collagen genes and TGF-βI signaling-related genes (Smad2 and Smad3) in muscle cells...
October 30, 2016: Veterinary Parasitology
https://www.readbyqxmd.com/read/27872188/a-monoclonal-antibody-to-cryptococcus-neoformans-glucuronoxylomannan-manifests-hydrolytic-activity-for-both-peptides-and-polysaccharides
#8
Anthony Bowen, Maggie P Wear, Radames Cordero, Stefan Oscarson, Arturo Casadevall
Studies in the 1980s first showed that some natural antibodies were "catalytic" and able to hydrolyze peptide or phosphodiester bonds in antigens. Many naturally occurring catalytic antibodies have since been isolated from human sera and associated with positive and negative outcomes in autoimmune disease and infection. The function and prevalence of these antibodies, however, remains unclear. A previous study suggested that the 18B7 monoclonal antibody against glucuronoxylomannan (GXM)--the major component of the Cryptococcus neoformans polysaccharide capsule--hydrolyzed a peptide antigen mimetic...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27867114/serine-protease-inhibitor-kazal-type-2-is-expressed-in-the-male-reproductive-tract-of-carp-with-a-possible-role-in-antimicrobial-protection
#9
Mariola A Dietrich, Mariola Słowińska, Halina Karol, Mikołaj Adamek, Dieter Steinhagen, Anna Hejmej, Barbara Bilińska, Andrzej Ciereszko
The presence of the low-molecular-mass serine protease inhibitor Kazal-type (Spink) is a characteristic feature of vertebrate semen. Its main function is control of the serine protease in the acrosome, acrosin. Here we showed for the first time that Spink is present in the seminal plasma of carp, which have anacrosomal spermatozoa. Using a three-step isolation procedure that consisted in gel filtration and RP-HPLC and re-RP-HPLC, we isolated this inhibitor and identified it as serine protease inhibitor Kazal-type 2 (Spink2), a reproductive-derived member of the Spink family...
November 17, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27855621/alpha-1-antitrypsin-deficiency-current-perspective-from-genetics-to-diagnosis-and-therapeutic-approaches
#10
Simona Santangelo, Simone Scarlata, Luana M Poeta, Adam J Bialas, Gregorino Paone, Raffaele Antonelli Incalzi
Alpha-1 antitrypsin (A1AT) is a 52-kDa, acute phase glycoprotein encoded by the protease inhibitor (PI) locus, located on the long arm of chromosome 14 (14q31-32.3). Its structure is composed of a total of 7 exons, 4 coding (II, III, IV, and V) and 3 non-coding (Ia, Ib, and Ic). A1AT is produced primarily by hepatocytes and acts as a serine protease inhibitor with anti-protease and immunoregulatory activities. The main target of A1AT is neutrophil elastase (NE), an enzyme released during a neutrophil-mediated inflammatory process...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27845447/novel-method-to-rescue-a-lethal-phenotype-through-integration-of-target-gene-onto-the-x-chromosome
#11
Kazuya Sakata, Kimi Araki, Hiroyasu Nakano, Takashi Nishina, Sachiko Komazawa-Sakon, Shin Murai, Grace E Lee, Daisuke Hashimoto, Chigure Suzuki, Yasuo Uchiyama, Kenji Notohara, Anna S Gukovskaya, Ilya Gukovsky, Ken-Ichi Yamamura, Hideo Baba, Masaki Ohmuraya
The loss-of-function mutations of serine protease inhibitor, Kazal type 1 (SPINK1) gene are associated with human chronic pancreatitis, but the underlying mechanisms remain unknown. We previously reported that mice lacking Spink3, the murine homologue of human SPINK1, die perinatally due to massive pancreatic acinar cell death, precluding investigation of the effects of SPINK1 deficiency. To circumvent perinatal lethality, we have developed a novel method to integrate human SPINK1 gene on the X chromosome using Cre-loxP technology and thus generated transgenic mice termed "X-SPINK1"...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27845251/heparan-sulfate-heparin-glycosaminoglycan-binding-alters-inhibitory-profile-and-enhances-anticoagulant-function-of-conserved-amblyomma-americanum-tick-saliva-serpin-19
#12
Željko M Radulović, Albert Mulenga
Some serine protease inhibitor (serpin) regulators of essential life pathways bind glycosaminoglycans (GAGs) to enhance inhibitory functions and achieve physiologically relevant rates. This study demonstrates that highly conserved Amblyomma americanum tick saliva serpin 19 (AAS19), a broad-spectrum inhibitor of hemostasis and inflammation system proteases and anticoagulant, can bind heparan sulfate/heparin (HS)GAGs and that this interaction alters its function. Substrate hydrolysis and unpaired t-test analyses revealed that HSGAG binding caused rAAS19 inhibitory activity to: (i) significantly increase against blood clotting factors (f) IIa (thrombin) and fIXa, (ii) significantly reduce against fXa and fXIIa and (iii) moderate to no effect against trypsin, kallikrein, papain, and plasmin...
November 12, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27836723/identification-and-functional-characterizations-of-serpin8-a-potential-prophenoloxidase-activating-protease-inhibitor-in-pacific-white-shrimp-litopenaeus-vannamei
#13
Yongjie Liu, Yuhang Sun, Qiai Wang, Fujun Hou, Xiaolin Liu
Serpins have been characterized from varieties of organisms by their inhibitory roles on serine or cysteine proteases. However, research for the functional study of serpins in crustacean is relatively small. To fully clarify the immune characterizations of serpin, a novel serpin (named Lvserpin8) encoding 414 amino acids with a 19-amino acid signal peptide and a serpin domain was identified from the Pacific white shrimp Litopenaeus vannamei. Sequence analysis indicated that the genomic Lvserpin8 gene contains 5 exons and 4 introns...
November 8, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27831584/the-development-of-small-molecule-modulators-for-clpp-protease-activity
#14
REVIEW
Fei Ye, Jiahui Li, Cai-Guang Yang
The global spread of antibiotic resistance among important human pathogens emphasizes the need to find new antibacterial drugs with a novel mode of action. The ClpP protease has been shown to demonstrate its pivotal importance to both the survival and the virulence of pathogenic bacteria during host infection. Deregulating ClpP activity either through overactivation or inhibition could lead to antibacterial activity, declaiming the dual molecular mechanism for small-molecule modulation. Recently, natural products acyldepsipeptides (ADEPs) have been identified as a new class of antibiotics that activate ClpP to a dysfunctional state in the absence of cognate ATPases...
November 10, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27830465/partial-characterization-of-the-proteolytic-properties-of-an-enzymatic-extract-from-aguama-bromelia-pinguin-l-fruit-grown-in-mexico
#15
Jesús Martín Moreno-Hernández, Xitlalli Desideria Hernández-Mancillas, Evelia Lorena Coss Navarrete, Miguel Ángel Mazorra-Manzano, Idalia Osuna-Ruiz, Víctor Alfonso Rodríguez-Tirado, Jesús Aarón Salazar-Leyva
Plant proteases are capable of performing several functions in biological systems, and their use is attractive for biotechnological process due to their interesting catalytic properties. Bromelia pinguin (aguama) is a wild abundant natural resource in several regions of Central America and the Caribbean Islands but is underutilized. Their fruits are rich in proteases with properties that are still unknown, but they represent an attractive source of enzymes for biotechnological applications. Thus, the proteolytic activity in enzymatic crude extracts (CEs) from wild B...
November 9, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27824929/tissue-kallikrein-inhibitors-based-on-the-sunflower-trypsin-inhibitor-scaffold-a-potential-therapeutic-intervention-for-skin-diseases
#16
Wenjie Chen, Veronica A Kinsler, Derek Macmillan, Wei-Li Di
Tissue kallikreins (KLKs), in particular KLK5, 7 and 14 are the major serine proteases in the skin responsible for skin shedding and activation of inflammatory cell signaling. In the normal skin, their activities are controlled by an endogenous protein protease inhibitor encoded by the SPINK5 gene. Loss-of-function mutations in SPINK5 leads to enhanced skin kallikrein activities and cause the skin disease Netherton Syndrome (NS). We have been developing inhibitors based on the Sunflower Trypsin Inhibitor 1 (SFTI-1) scaffold, a 14 amino acids head-to-tail bicyclic peptide with a disulfide bond...
2016: PloS One
https://www.readbyqxmd.com/read/27820798/dpp8-and-dpp9-inhibition-induces-pro-caspase-1-dependent-monocyte-and-macrophage-pyroptosis
#17
Marian C Okondo, Darren C Johnson, Ramya Sridharan, Eun Bin Go, Ashley J Chui, Mitchell S Wang, Sarah E Poplawski, Wengen Wu, Yuxin Liu, Jack H Lai, David G Sanford, Michael O Arciprete, Todd R Golub, William W Bachovchin, Daniel A Bachovchin
Val-boroPro (Talabostat, PT-100), a nonselective inhibitor of post-proline cleaving serine proteases, stimulates mammalian immune systems through an unknown mechanism of action. Despite this lack of mechanistic understanding, Val-boroPro has attracted substantial interest as a potential anticancer agent, reaching phase 3 trials in humans. Here we show that Val-boroPro stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. We demonstrate that the inhibition of two serine proteases, DPP8 and DPP9, activates the pro-protein form of caspase-1 independent of the inflammasome adaptor ASC...
November 7, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27818099/how-dextran-sulfate-affects-c1-inhibitor-activity-a-model-for-polysaccharide-potentiation
#18
Madelon Dijk, Jolande Holkers, Patrick Voskamp, Bruno M Giannetti, Willem-Jan Waterreus, Harrie A van Veen, Navraj S Pannu
C1-inhibitor is a key inhibitor of the complement and contact activation systems, and mutations in the protein can cause hereditary angioedema. Through an unknown mechanism, polysaccharides can increase C1-inhibitor activity against some of its target proteases. Here we present the crystal structures of the serine protease inhibitor (serpin) domain of active C1-inhibitor by itself and in complex with dextran sulfate. Unlike previously described interactions of serpins with polysaccharides, the structures and isothermal titration calorimetry experiments together reveal that dextran sulfate binds to C1-inhibitor's F1 helix with low affinity and does not invoke an allosteric change...
October 28, 2016: Structure
https://www.readbyqxmd.com/read/27813674/induction-of-tissue-factor-pathway-inhibitor-2-by-hcg-regulates-periovulatory-gene-expression-and-plasmin-activity
#19
Muraly Puttabyatappa, Linah F Al-Alem, Farnosh Zakerkish, Katherine L Rosewell, Mats Brännström, Thomas E Curry
A key event during the process of ovulation is an increased proteolytic activity that aids in breakdown of the follicular wall to permit oocyte release. How the activity of these proteases is regulated is still not known. We hypothesize that Tissue Factor Pathway Inhibitor 2 (TFPI2), a matrix-associated Kunitz-type serine protease inhibitor, plays a role in regulating proteolytic activity during the periovulatory period as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling...
November 4, 2016: Endocrinology
https://www.readbyqxmd.com/read/27808430/collagenase-produced-from-aspergillus-sp-ucp-1276-using-chicken-feather-industrial-residue
#20
Catarina Michelle Oliveira Ferreira, Patyanne Carvalho Correia, Romero Marcos Pedrosa Brandão-Costa, Wendell Wagner Campos Albuquerque, Tatiana Pereira Shin Liu, Galba Maria Campos-Takaki, Ana Lúcia Figueiredo Porto
An extracellular collagenolytic serine protease was purified from Aspergillus sp., isolated from the Caatinga biome in northeast Brazil by a two-step chromatographic procedure, using an anion-exchanger and gel filtration. The enzyme was produced by submerged fermentation of feather residue as a substrate. The purified collagenase showed a 2.09-fold increase in specific activity and 22.85% yield. The enzyme was a monomeric protein with a molecular mass of 28.7 kDa, estimated by SDS-PAGE and AKTA system. The optimum temperature and pH for enzyme activity were around 40 °C and pH 8...
November 3, 2016: Biomedical Chromatography: BMC
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