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Proteolytic enzymes

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https://www.readbyqxmd.com/read/28088524/possible-roles-of-the-transcription-factor-nrf1-nfe2l1-in-neural-homeostasis-by-regulating-the-gene-expression-of-deubiquitinating-enzymes
#1
Hiroaki Taniguchi, Shota Okamuro, Misaki Kohji, Tsuyoshi Waku, Kaori Kubo, Atsushi Hatanaka, Yimeng Sun, A M Masudul Azad Chowdhury, Akiyoshi Fukamizu, Akira Kobayashi
The transcription factor Nrf1 (NFE2L1) maintains protein homeostasis (proteostasis) by regulating the gene expression of proteasome subunits in response to proteasome inhibition. The deletion of the Nrf1 gene in neural stem/progenitor cells causes severe neurodegeneration due to the accumulation of ubiquitinated proteins in Purkinje cells and motor neurons (Nrf1 NKO mice). However, the molecular mechanisms governing this neurodegenerative process remain unclear. We demonstrate herein that the loss of Nrf1 leads to the reduced gene expression of the deubiquitinating enzymes (DUBs) but not proteasome subunits in Nrf1 NKO mice between P7 and P18...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088271/adamts-3-13-16-and-19-levels-in-patients-with-habitual-abortion
#2
Meryem Kuru Pekcan, Esma Sarıkaya, Aytekin Tokmak, Murat Alışık, Afra Alkan, Gülnur Özakşit, Özcan Erel
A disintegrin-like and metalloproteinase domain with thrombospondin-type 1 motifs (ADAMTS) protein superfamily includes 19 secreted metalloproteases. Proteolytic substrates of ADAMTS enzymes have been linked to reproductive function. The aim of this study was to investigate serum ADAMTS-3, -13, -16, and -19 levels in women with habitual abortions compared with those in healthy controls. A total of 86 women were enrolled in this prospective case-control study. ADAMTS-3, -13, -16, and -19 values were recorded and analyzed in association with demographic and clinical parameters...
January 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28087531/salivary-gluten-degradation-and-oral-microbial-profiles-in-health-and-celiac-disease
#3
Na Tian, Lina Faller, Daniel A Leffler, Ciaran P Kelly, Joshua Hansen, Jos A Bosch, Guoxian Wei, Bruce J Paster, Detlef Schuppan, Eva J Helmerhorst
: Celiac disease (CD) is a chronic immune-mediated enteropathy induced by dietary gluten in genetically predisposed individuals. Saliva harbors the second highest bacterial load of the GI tract after the colon. Moreover, saliva contains gluten-degrading enzymes produced by oral bacteria that may modify gluten processing in the intestine and susceptibility to celiac disease (CD). AIM: To investigate salivary enzymatic activities and oral microbial profiles in healthy subjects vs patients with classical and refractory CD...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#4
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28076816/mutation-g1629e-increases-von-willebrand-factor-cleavage-via-a-cooperative-destabilization-mechanism
#5
Camilo Aponte-Santamaría, Svenja Lippok, Judith J Mittag, Tobias Obser, Reinhard Schneppenheim, Carsten Baldauf, Frauke Gräter, Ulrich Budde, Joachim O Rädler
The large multimeric glycoprotein von Willebrand Factor (VWF) plays a pivotal adhesive role during primary hemostasis. VWF is cleaved by the protease ADAMTS13 as a down-regulatory mechanism to prevent excessive VWF-mediated platelet aggregation. For each VWF monomer, the ADAMTS13 cleavage site is located deeply buried inside the VWF A2 domain. External forces in vivo or denaturants in vitro trigger the unfolding of this domain, thereby leaving the cleavage site solvent-exposed and ready for cleavage. Mutations in the VWF A2 domain, facilitating the cleavage process, cause a distinct form of von Willebrand disease (VWD), VWD type 2A...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28069606/proteolytic-properties-of-single-chain-factor-xii-a-mechanism-for-triggering-contact-activation
#6
Ivan Ivanov, Anton Matafonov, Mao-Fu Sun, Qiufang Cheng, S Kent Dickeson, Ingrid M Verhamme, Jonas Emsley, David Gailani
When blood is exposed to variety of artificial surfaces and biologic substances, the plasma proteins factor XII (FXII) and prekallikrein undergo reciprocal proteolytic conversion to the proteases αFXIIa and α-kallikrein by a process called contact activation. These enzymes contribute to host-defense responses including coagulation, inflammation, and fibrinolysis. The initiating event in contact activation is debated. To test the hypothesis that single-chain FXII expresses activity that could initiate contact activation, we prepared human FXII variants lacking the Arg353 cleavage site required for conversion to αFXIIa (FXII-R353A), or lacking the three known cleavage sites at Arg334, Arg343, and Arg353 (FXII-T, for "triple" mutant), and compared their properties to wild type αFXIIa...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28065272/activity-assays-for-rhomboid-proteases
#7
E Arutyunova, K Strisovsky, M J Lemieux
Rhomboids are ubiquitous intramembrane serine proteases that are involved in various signaling pathways. This fascinating class of proteases harbors an active site buried within the lipid milieu. High-resolution structures of the Escherichia coli rhomboid GlpG with various inhibitors revealed the catalytic mechanism for rhomboid-mediated proteolysis; however, a quantitative characterization was lacking. Assessing an enzyme's catalytic parameters is important for understanding the details of its proteolytic reaction and regulatory mechanisms...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28065265/an-inducible-reconstitution-system-for-the-real-time-kinetic-analysis-of-protease-activity-and-inhibition-inside-the-membrane
#8
R P Baker, S Urban
Intramembrane proteases are an ancient and diverse group of multispanning membrane proteins that cleave transmembrane substrates inside the membrane to effect a wide range of biological processes. As proteases, a clear understanding of their function requires kinetic dissection of their catalytic mechanism, but this is difficult to achieve for membrane proteins. Kinetic measurements in detergent systems are complicated by micelle fusion/exchange, which introduces an additional kinetic step and imposes system-specific behaviors (e...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28065263/probing-the-structure-and-function-relationships-of-presenilin-by-substituted-cysteine-accessibility-method
#9
T Tomita
Presenilin is a catalytic subunit of γ-secretase, which hydrolyzes several transmembrane proteins within the lipid bilayer, together with binding cofactors such as nicastrin, Aph-1, and Pen-2. However, the structural basis as well as molecular mechanism of this unusual proteolytic process remains unknown. We have analyzed the structure and function relationships of presenilin using the substituted-cysteine accessibility method (SCAM), which enables identification of the hydrophilic environment by the accessibility of sulfhydryl reagents to cysteine residues introduced at a desired position...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28058488/inhibition-of-staphylococcus-aureus-in-vitro-by-bacteriocinogenic-lactococcus-lactis-kth0-1s-isolated-from-thai-fermented-shrimp-kung-som-and-safety-evaluation
#10
Sutanate Saelao, Suppasil Maneerat, Sireewan Kaewsuwan, Hanitra Rabesona, Yvan Choiset, Thomas Haertlé, Jean-Marc Chobert
Lactococcus lactis KTH0-1S isolated from Thai traditional fermented shrimp (Kung-som) is able to produce heat-stable bacteriocin and inhibits food spoilage bacteria and food-borne pathogens. The inhibitory effect of bacteriocin remained intact after treatment with different pHs and after heating, but was sensitive to some proteolytic enzymes. Addition of bacteriocin KTH0-1S to Staphylococcus aureus cultures decreased viable cell counts by 2.8 log CFU/ml, demonstrating a bactericidal mode of action. Furthermore, the growth of S...
January 5, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28056193/reduced-cd62l-expression-on-t-cells-and-increased-soluble-cd62l-levels-predict-molecular-response-to-tyrosine-kinase-inhibitor-therapy-in-early-chronic-phase-chronic-myelogenous-leukemia
#11
Sieghart Sopper, Satu Mustjoki, Deborah White, Timothy Hughes, Peter Valent, Andreas Burchert, Bjørn T Gjertsen, Günther Gastl, Matthias Baldauf, Zlatko Trajanoski, Frank Giles, Andreas Hochhaus, Thomas Ernst, Thomas Schenk, Jeroen J W M Janssen, Gert J Ossenkoppele, Kimmo Porkka, Dominik Wolf
Purpose Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. Patients and Methods A prospective and comprehensive flow cytometry-based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-naïve patients with chronic-phase CML. Data were verified in independent validation cohorts...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28052575/emerging-challenges-in-the-design-of-selective-protease-substrates-inhibitors-and-activity-based-probes-for-indistinguishable-proteases
#12
REVIEW
Paulina Kasperkiewicz, Marcin Poreba, Katarzyna Groborz, Marcin Drag
Proteases are enzymes that hydrolyze the peptide bond of peptide substrates and proteins. Despite significant progress in recent years, one of the greatest challenges in the design and testing of substrates, inhibitors and activity-based probes (ABPs) for proteolytic enzymes is achieving specificity toward only one enzyme. This specificity is particularly important if the enzyme is present with other enzymes with a similar catalytic mechanism and substrate specificity but completely different functionality...
January 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28050857/secondary-metabolites-from-bacillus-amyloliquefaciens-isolated-from-soil-can-kill-burkholderia-pseudomallei
#13
Patcharaporn Boottanun, Chotima Potisap, Julian G Hurdle, Rasana W Sermswan
Bacillus species are Gram-positive bacteria found in abundance in nature and their secondary metabolites were found to possess various potential activities, notably antimicrobial. In this study, Bacillus amyloliquefaciens N2-4 and N3-8 were isolated from soil and their metabolites could kill Burkholderia pseudomallei, a Gram-negative pathogenic bacterium also found in soil in its endemic areas. Moreover, the metabolites were able to kill drug resistant isolates of B. pseudomallei and also inhibit other pathogenic bacteria such as Staphylococcus aureus, Escherichia coli and Acinetobacter baumannii but not the non-pathogenic Burkholderia thailandensis, which is closely related to B...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28042769/discovery-of-an-unexplored-protein-structural-scaffold-of-serine-protease-from-big-blue-octopus-octopus-cyanea-a-new-prospective-lead-molecule
#14
Subhamay Panda, Leena Kumari
BACKGROUND: Serine proteases are a group of enzymes that hydrolyses the peptide bonds in proteins. In mammals, these enzymes help in the regulation of several major physiological functions such as digestion, blood clotting, responses of immune system, reproductive functions and the complement system. OBJECTIVE: Serine proteases obtained from the venom of Octopodidae family is a relatively unexplored area of research. In the present work, we tried to effectively utilize comparative composite molecular modeling technique...
January 2, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28035757/papp-a-a-promising-therapeutic-target-for-healthy-longevity
#15
REVIEW
Cheryl A Conover, Claus Oxvig
Pregnancy-associated plasma protein-A (PAPP-A) is a proteolytic enzyme that was discovered to increase local insulin-like growth factor (IGF) availability for receptor activation through cleavage of inhibitory IGF binding proteins (IGFBPs). Reduced IGF signaling has been associated with increased lifespan and healthspan. Therefore, inhibition of PAPP-A represents a novel approach to indirectly decrease the availability of bioactive IGF. Here, we will review data in support of PAPP-A as a therapeutic target to promote healthy longevity...
December 29, 2016: Aging Cell
https://www.readbyqxmd.com/read/28031280/proteolytic-cleavage-of-the-immunodominant-outer-membrane-protein-rompa-in-rickettsia-rickettsii
#16
Nicholas F Noriea, Tina R Clark, David Mead, Ted Hackstadt
: Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, contains two immunodominant proteins, rOmpA and rOmpB, in the outer membrane. Both rOmpA and rOmpB are conserved throughout spotted fever group rickettsiae as members of a family of autotransporter proteins. Previously, it was demonstrated that rOmpB is proteolytically processed with the cleavage site residing near the autotransporter domain at the carboxy-terminal end of the protein, cleaving the 168 kDa precursor into apparent 120 kDa and 32 kDa fragments...
December 28, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/28026803/-furin-as-proprotein-convertase-and-its-role-in-normaland-pathological-biological-processes
#17
REVIEW
N I Solovyeva, T A Gureeva, O S Timoshenko, T A Moskvitina, E V Kugaevskaya
Furin belongs to serine intracellular Ca2+-dependent endopeptidases of the subtilisin family, also known as proprotein convertase (PC). Human furin is synthesized as zymogen with a molecular weight of 104 kDà, which is then activated by autocatalytic in two stages. This process can occur when zymogen migrates from the endoplasmic reticulum to the Golgi apparatus, where a large part of furin is accumulated. The molecular weigh t of the active furin is 98 kDà. Furin relates to enzymes with a narrow substrate specificity: it hydrolyzes peptide bonds at the site of paired basic amino acids and furin activity exhibits in a wide pH range 5-8...
November 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28019702/alkaline-serine-proteases-from-helicoverpa-armigera-potential-candidates-for-industrial-applications
#18
Shaik Mohammad Akbar, Hari Chand Sharma
We characterized trypsin- and chymotrypsin-like serine alkaline proteases from cotton bollworm, Helicoverpa armigera, for their probable potential application as additives in various bio-formulations. Purification was achieved by using hydroxylapatite, DEAE sephadex and CM sephadex columns, which resulted in increased enzyme activity by 13.76- and 14.05-fold for trypsin and chymotrypsin, respectively. Michaelis-Menten constants (Km ) for substrates of trypsin and chymotrypsin, BApNA and SAAPFpNA, were found to be 1...
December 26, 2016: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28018312/enzyme-mediated-quenching-of-the-pseudomonas-quinolone-signal-pqs-promotes-biofilm-formation-of-pseudomonas-aeruginosa-by-increasing-iron-availability
#19
Beatrix Tettmann, Christine Niewerth, Frank Kirschhöfer, Anke Neidig, Andreas Dötsch, Gerald Brenner-Weiss, Susanne Fetzner, Joerg Overhage
The 2-alkyl-3-hydroxy-4(1H)-quinolone 2,4-dioxygenase HodC was previously described to cleave the Pseudomonas quinolone signal, PQS, which is exclusively used in the complex quorum sensing (QS) system of Pseudomonas aeruginosa, an opportunistic pathogen employing QS to regulate virulence and biofilm development. Degradation of PQS by exogenous addition of HodC to planktonic cells of P. aeruginosa attenuated production of virulence factors, and reduced virulence in planta. However, proteolytic cleavage reduced the efficacy of HodC...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28011710/identification-of-novel-loci-affecting-circulating-chromogranins-and-related-peptides
#20
Beben Benyamin, Adam X Maihofer, Andrew J Schork, Bruce A Hamilton, Fangwen Rao, Geert W Schmid-SchÖnbein, Kuixing Zhang, Manjula Mahata, Mats Stridsberg, Nicholas J Schork, Nilima Biswas, Vivian Y Hook, Zhiyun Wei, Grant W Montgomery, Nicholas G Martin, Caroline M Nievergelt, John B Whitfield, Daniel T O'Connor
Chromogranins are pro-hormone secretory proteins released from neuroendocrine cells, with effects on control of blood pressure. We conducted a genome-wide association study for plasma catestatin, the catecholamine release inhibitory peptide derived from chromogranin A (CHGA), and other CHGA- or chromogranin B (CHGB)-related peptides, in 545 US and 1252 Australian subjects. This identified loci on chromosomes 4q35 and 5q34 affecting catestatin concentration (p=3.40 x 10(-30) for rs4253311 and 1.85 x 10(-19) for rs2731672, respectively)...
December 22, 2016: Human Molecular Genetics
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