DOCSLIB.ORG

What Is a Protease?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
What Is a Protease? What is a Protease? Proteases (or peptidases) are enzymes secreted by animals for a number of physiological processes, among which is the Dr. Rolando A. Valientes digestion of feed protein. Regional Category Manager- Animals normally secrete suffi - Eubiotics / RONOZYME ProAct cient amount of enzymes to ade - Asia Pacific, DSM quately digest enough of their [email protected] feed so that they grow and remain healthy under normal conditions, such as those found in the wild. Any increased needs for protein (amino acids) for more rapid growth due to improved genetics has been traditionally met by adding more protein (or synthetic amino acids) into the feed. This was facilitated by a relative low cost for most protein-rich ingredi - Dr. Katrine Pontoppidan ents, such as soybean meal, and Research Scientist synthetic amino acids, such as Novozymes L-lysine HCL. Thus, an exogenous [email protected] protease (as a feed supplement) was not considered essential; that is, until recently. size, the rate of passage of feed Today we face not only the prob - through the digestive tract, the lem of feeding animals of continu - age of the animal, and its physio - ously increasing genetic potential logical/health condition. All of (this requires diets increasingly these variables are rather difficult richer in amino acids), but also an to control, but supplementing unprecedented rise in ingredient animal feeds with extra enzymes prices, leaving very small (if any) is rather easy if it can be done in a margin for profitability. Thus, it profitable way. has been deemed essential to seek ways to improve the nutritive Up until recently, any protease value of existing ingredients activity in commercial enzyme reducing feed cost. Naturally, cocktails was part of unavoidable protein, being the second most by-products from the production expensive feed com ponent, has of other enzymes. Fortunately in received considerable attention 2008, DSM launched a pure worldwide. This has been aided (mono-component) protease ® by the negative public image of (RONOZYME ProAct) that can be animal residues, which if rich in used with any protein source and nitrogen (basic component of all in any type of formulation, even proteins) constitute a potential with low-protein diets! Results environmental hazard. based on a number of scientific papers indicated that this pro - Here it should be noted that tease enhances protein digestion natural feed proteins are never by about 4% (depending on the 100% digested by any animal. For specific amino acid under ques - monogastric species, protein in tion this number can be higher or soybean meal is about 87% lower). Empirical data from com - digestible, whereas protein in mercial broiler farms has shown maize is only 81% digestible; the that the use of this enzyme in rest reaches the environment. 'protein reduced' diets can Thus, there is a significant part of improve profitability by feed protein that is clearly being 2 euro-cents per broiler (after wasted, instead of being used for taking into account the cost of the production of meat, eggs, and enzyme)! Benefits from reducing milk. The reasons for this ineffi - the emission of ammonia into the ciency are varied and include (but environment further enhance the are not limited to) feed particle value of this protease. E005A.
Load more

Recommended publications
  • Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin
    The Journal of Neuroscience, March 22, 2017 • 37(12):3181–3191 • 3181 Cellular/Molecular Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin Himari Ogino,1* Arisa Hisanaga,1* XTakao Kohno,1 Yuta Kondo,1 Kyoko Okumura,1 Takana Kamei,1 Tempei Sato,2 Hiroshi Asahara,2 Hitomi Tsuiji,1 Masaki Fukata,3 and Mitsuharu Hattori1 1Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan, 2Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan, and 3Division of Membrane Physiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer’s disease; however, noninvasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo. Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons. This enzyme was identified as a disintegrin and metalloproteinase with thrombospondin motifs-3 (ADAMTS-3). Recombinant ADAMTS-3 cleaved Reelin at the N-t site. ADAMTS-3 was expressed in excitatory neurons in the cerebral cortex and hippocampus.
    [Show full text]
  • The Involvement of Cysteine Proteases and Protease Inhibitor Genes in the Regulation of Programmed Cell Death in Plants
    The Plant Cell, Vol. 11, 431–443, March 1999, www.plantcell.org © 1999 American Society of Plant Physiologists The Involvement of Cysteine Proteases and Protease Inhibitor Genes in the Regulation of Programmed Cell Death in Plants Mazal Solomon,a,1 Beatrice Belenghi,a,1 Massimo Delledonne,b Ester Menachem,a and Alex Levine a,2 a Department of Plant Sciences, Hebrew University of Jerusalem, Givat-Ram, Jerusalem 91904, Israel b Istituto di Genetica, Università Cattolica S.C., Piacenza, Italy Programmed cell death (PCD) is a process by which cells in many organisms die. The basic morphological and bio- chemical features of PCD are conserved between the animal and plant kingdoms. Cysteine proteases have emerged as key enzymes in the regulation of animal PCD. Here, we show that in soybean cells, PCD-activating oxidative stress in- duced a set of cysteine proteases. The activation of one or more of the cysteine proteases was instrumental in the PCD of soybean cells. Inhibition of the cysteine proteases by ectopic expression of cystatin, an endogenous cysteine pro- tease inhibitor gene, inhibited induced cysteine protease activity and blocked PCD triggered either by an avirulent strain of Pseudomonas syringae pv glycinea or directly by oxidative stress. Similar expression of serine protease inhib- itors was ineffective. A glutathione S-transferase–cystatin fusion protein was used to purify and characterize the in- duced proteases. Taken together, our results suggest that plant PCD can be regulated by activity poised between the cysteine proteases and the cysteine protease inhibitors. We also propose a new role for proteinase inhibitor genes as modulators of PCD in plants.
    [Show full text]
  • Chapter 11 Cysteine Proteases
    CHAPTER 11 CYSTEINE PROTEASES ZBIGNIEW GRZONKA, FRANCISZEK KASPRZYKOWSKI AND WIESŁAW WICZK∗ Faculty of Chemistry, University of Gdansk,´ Poland ∗[email protected] 1. INTRODUCTION Cysteine proteases (CPs) are present in all living organisms. More than twenty families of cysteine proteases have been described (Barrett, 1994) many of which (e.g. papain, bromelain, ficain , animal cathepsins) are of industrial impor- tance. Recently, cysteine proteases, in particular lysosomal cathepsins, have attracted the interest of the pharmaceutical industry (Leung-Toung et al., 2002). Cathepsins are promising drug targets for many diseases such as osteoporosis, rheumatoid arthritis, arteriosclerosis, cancer, and inflammatory and autoimmune diseases. Caspases, another group of CPs, are important elements of the apoptotic machinery that regulates programmed cell death (Denault and Salvesen, 2002). Comprehensive information on CPs can be found in many excellent books and reviews (Barrett et al., 1998; Bordusa, 2002; Drauz and Waldmann, 2002; Lecaille et al., 2002; McGrath, 1999; Otto and Schirmeister, 1997). 2. STRUCTURE AND FUNCTION 2.1. Classification and Evolution Cysteine proteases (EC.3.4.22) are proteins of molecular mass about 21-30 kDa. They catalyse the hydrolysis of peptide, amide, ester, thiol ester and thiono ester bonds. The CP family can be subdivided into exopeptidases (e.g. cathepsin X, carboxypeptidase B) and endopeptidases (papain, bromelain, ficain, cathepsins). Exopeptidases cleave the peptide bond proximal to the amino or carboxy termini of the substrate, whereas endopeptidases cleave peptide bonds distant from the N- or C-termini. Cysteine proteases are divided into five clans: CA (papain-like enzymes), 181 J. Polaina and A.P. MacCabe (eds.), Industrial Enzymes, 181–195.
    [Show full text]
  • Proteolytic Cleavage—Mechanisms, Function
    Review Cite This: Chem. Rev. 2018, 118, 1137−1168 pubs.acs.org/CR Proteolytic CleavageMechanisms, Function, and “Omic” Approaches for a Near-Ubiquitous Posttranslational Modification Theo Klein,†,⊥ Ulrich Eckhard,†,§ Antoine Dufour,†,¶ Nestor Solis,† and Christopher M. Overall*,†,‡ † ‡ Life Sciences Institute, Department of Oral Biological and Medical Sciences, and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada ABSTRACT: Proteases enzymatically hydrolyze peptide bonds in substrate proteins, resulting in a widespread, irreversible posttranslational modification of the protein’s structure and biological function. Often regarded as a mere degradative mechanism in destruction of proteins or turnover in maintaining physiological homeostasis, recent research in the field of degradomics has led to the recognition of two main yet unexpected concepts. First, that targeted, limited proteolytic cleavage events by a wide repertoire of proteases are pivotal regulators of most, if not all, physiological and pathological processes. Second, an unexpected in vivo abundance of stable cleaved proteins revealed pervasive, functionally relevant protein processing in normal and diseased tissuefrom 40 to 70% of proteins also occur in vivo as distinct stable proteoforms with undocumented N- or C- termini, meaning these proteoforms are stable functional cleavage products, most with unknown functional implications. In this Review, we discuss the structural biology aspects and mechanisms
    [Show full text]
  • Intrinsic Evolutionary Constraints on Protease Structure, Enzyme
    Intrinsic evolutionary constraints on protease PNAS PLUS structure, enzyme acylation, and the identity of the catalytic triad Andrew R. Buller and Craig A. Townsend1 Departments of Biophysics and Chemistry, The Johns Hopkins University, Baltimore MD 21218 Edited by David Baker, University of Washington, Seattle, WA, and approved January 11, 2013 (received for review December 6, 2012) The study of proteolysis lies at the heart of our understanding of enzyme evolution remain unanswered. Because evolution oper- biocatalysis, enzyme evolution, and drug development. To un- ates through random forces, rationalizing why a particular out- derstand the degree of natural variation in protease active sites, come occurs is a difficult challenge. For example, the hydroxyl we systematically evaluated simple active site features from all nucleophile of a Ser protease was swapped for the thiol of Cys at serine, cysteine and threonine proteases of independent lineage. least twice in evolutionary history (9). However, there is not This convergent evolutionary analysis revealed several interre- a single example of Thr naturally substituting for Ser in the lated and previously unrecognized relationships. The reactive protease catalytic triad, despite its greater chemical similarity rotamer of the nucleophile determines which neighboring amide (9). Instead, the Thr proteases generate their N-terminal nu- can be used in the local oxyanion hole. Each rotamer–oxyanion cleophile through a posttranslational modification: cis-autopro- hole combination limits the location of the moiety facilitating pro- teolysis (10, 11). These facts constitute clear evidence that there ton transfer and, combined together, fixes the stereochemistry of is a strong selective pressure against Thr in the catalytic triad that catalysis.
    [Show full text]
  • Cathepsin G and Its Role in Inflammation and Autoimmune Diseases
    Arch Rheumatol 2018;33(4):498-504 doi: 10.5606/ArchRheumatol.2018.6595 REVIEW Cathepsin G and Its Role in Inflammation and Autoimmune Diseases Siming GAO, Honglin ZHU, Xiaoxia ZUO, Hui LUO Department of Rheumatology, Xiangya Hospital, Hunan, China ABSTRACT Cathepsin G belongs to the neutrophil serine proteases family, known for its function in killing pathogens. Studies over the past several years indicate that cathepsin G has important effects on inflammation and immune reaction, and may be a key factor in the pathogenesis of some autoimmune diseases. In this article, we discuss the roles of cathepsin G in inflammation, immune reaction, and autoimmune diseases. To our knowledge, this is the first study providing important information about cathepsin G in the pathogenesis of autoimmune diseases and suggesting that cathepsin G may be a new biomarker or treatment target. Keywords: Autoimmune disease; cathepsin G; immune reaction; inflammation. Cathepsin G (CTSG) is a member of the serine two active forms of CTSG.9 Released CTSG can proteases family, which was first found in the evade its inhibitors, which exist in the extracellular azurophilic granules of neutrophil leukocytes space, by binding to cell membranes, forming and named in 1976.1,2 Then, CTSG was sequestered microenvironments, binding to its detected in other myeloid cells, such as B cells, substrates tightly, and inactivating its inhibitors.10 primary human monocytes, myeloid dendritic Cathepsin G has many functions. It can clear cells, plasmacytoid dendritic cells, and murine pathogens, regulate inflammation by modifying the 3 microglia. Recently, studies proved that CTSG chemokines, cytokines, cell surface receptors,11-14 also existed in neutrophil traps and human urine and C components,1 control the blood pressure, 4,5 exosomes.
    [Show full text]
  • Was the Serine Protease Cathepsin G Discovered by S. G. Hedin in 1903
    Vol. 58, No 1/2011 39–44 on-line at: www.actabp.pl Regular paper Was the serine protease cathepsin G discovered by S. G. Hedin in 1903 in bovine spleen? David Palesch1, Marcin Sieńczyk2, Jozef Oleksyszyn2, Michael Reich1, Ewa Wieczerzak3, Bernhard O. Boehm1 and Timo Burster1* 1Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany; 2Wrocław University of Technology, Wrocław, Poland; 3Faculty of Chemistry, University of Gdansk, Gdańsk, Poland In the beginning of the 20th century, enzymes with pro- tive under acidic conditions, which he named b-protease teolytic activity were classified as peptidases, Erepsin, (Hedin, 1903a). and proteases. Among these, pepsin, trypsin, and auto- lytic enzymes were of the protease class. Spleen-derived After discovering these two proteases in bovine proteases were poorly characterized until Sven Gustaf spleen, Hedin performed further experiments with bo- Hedin performed several digestion experiments with vine serum and concluded that it contained a weak pro- bovine spleen. He incubated minced bovine spleen un- teolytic enzyme active in neutral medium, the activity of der acidic or neutral conditions and characterized two which could be blocked by heating at 55 °C or neutral- active proteases; the results were published in 1903. ized by antibodies (also named anti-enzymes at the time) The first protease was named α-protease and was ac- present in the serum. Hedin assumed that the α-protease tive under neutral conditions. The second was named in bovine spleen-derived leukocytes was similar to the β-protease and was active under acidic conditions. We protease found in serum.
    [Show full text]
  • Correlation of Tumor Growth Suppression and Methionine Aminopetidase-2 Activity Blockade Using an Orally Active Inhibitor
    Correlation of tumor growth suppression and methionine aminopetidase-2 activity blockade using an orally active inhibitor Jieyi Wang*, Lora A. Tucker, Jason Stavropoulos, Qian Zhang, Yi-Chun Wang, Gail Bukofzer, Amanda Niquette, Jonathan A. Meulbroek, David M. Barnes, Jianwei Shen, Jennifer Bouska, Cherrie Donawho, George S. Sheppard, and Randy L. Bell Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 Edited by Brian W. Matthews, University of Oregon, Eugene, OR, and approved December 20, 2007 (received for review September 17, 2007) This laboratory and others have shown that agents that inhibit the in constitutively expressed (7, 8). More recently, MetAP1 has been vitro catalytic activity of methionine aminopeptidase-2 (MetAP2) are shown to play a role in the G2/M phase of cell cycle (9), whereas effective in blocking angiogenesis and tumor growth in preclinical MetAP2 inhibition leads to G1 arrest (10–12). models. However, these prototype MetAP2 inhibitors are clearly not Many of the details of the function of MetAP2 and its role in cell optimized for therapeutic use in the clinic. We have discovered an physiology are still unknown. In addition to its methionine amino- orally active class of MetAP2 inhibitors, the anthranilic acid sulfon- peptidase activity, MetAP2 has a second function: the stabilization amides exemplified by A-800141, which is highly specific for MetAP2. of eIF-2␣ phosphorylation status (8). That MetAP2 is a bifunc- This orally bioavailable inhibitor exhibits an antiangiogenesis effect tional protein complicates the study of its function with deletion or and a broad anticancer activity in a variety of tumor xenografts siRNA techniques, because the eIF-2␣ has an important role in including B cell lymphoma, neuroblastoma, and prostate and colon controlling protein synthesis and cell growth (8).
    [Show full text]
  • Plant Serine Protease Inhibitors: Biotechnology Application in Agriculture and Molecular Farming
    International Journal of Molecular Sciences Review Plant Serine Protease Inhibitors: Biotechnology Application in Agriculture and Molecular Farming Marina Clemente *, Mariana G. Corigliano, Sebastián A. Pariani, Edwin F. Sánchez-López, Valeria A. Sander and Víctor A. Ramos-Duarte Instituto Tecnológico Chascomús (INTECH), UNSAM-CONICET, Chascomús, Provincia de Buenos Aires B7130, Argentina; [email protected] (M.G.C.); [email protected] (S.A.P.); [email protected] (E.F.S.-L.); [email protected] (V.A.S.); [email protected] (V.A.R.-D.) * Correspondence: [email protected] Received: 12 January 2019; Accepted: 18 February 2019; Published: 17 March 2019 Abstract: The serine protease inhibitors (SPIs) are widely distributed in living organisms like bacteria, fungi, plants, and humans. The main function of SPIs as protease enzymes is to regulate the proteolytic activity. In plants, most of the studies of SPIs have been focused on their physiological role. The initial studies carried out in plants showed that SPIs participate in the regulation of endogenous proteolytic processes, as the regulation of proteases in seeds. Besides, it was observed that SPIs also participate in the regulation of cell death during plant development and senescence. On the other hand, plant SPIs have an important role in plant defense against pests and phytopathogenic microorganisms. In the last 20 years, several transgenic plants over-expressing SPIs have been produced and tested in order to achieve the increase of the resistance against pathogenic insects. Finally, in molecular farming, SPIs have been employed to minimize the proteolysis of recombinant proteins expressed in plants. The present review discusses the potential biotechnological applications of plant SPIs in the agriculture field.
    [Show full text]
  • The Cysteine Protease–Cysteine Protease Inhibitor System Explored in Soybean Nodule Development
    Agronomy 2013, 3, 550-570; doi:10.3390/agronomy3030550 OPEN ACCESS agronomy ISSN 2073-4395 www.mdpi.com/journal/agronomy Discussion The Cysteine Protease–Cysteine Protease Inhibitor System Explored in Soybean Nodule Development Barend Juan Vorster 1,†, Urte Schlüter 2,†, Magdeleen du Plessis 1, Stefan van Wyk 1, Matome Eugene Makgopa 2, Ignatious Ncube 3, Marian Dorcas Quain 4, Karl Kunert 2 and Christine Helen Foyer 4,* 1 Department of Plant Production and Soil Science, Forestry and Agricultural Biotechnology Institute, University of Pretoria, Pretoria 0002, South Africa; E-Mails: [email protected] (B.J.V.); [email protected] (M.P.); [email protected] (S.W.) 2 Department of Plant Science, Forestry and Agricultural Biotechnology Institute, University of Pretoria, Pretoria 0002, South Africa; E-Mails: [email protected] (U.S.); [email protected] (M.E.M.); [email protected] (K.K.) 3 Biotechnology Unit School of Molecular and Life Sciences, University of Limpopo, Sovenga 0727, South Africa; E-Mail: [email protected] 4 Center for Plant Sciences, Faculty of Biology, University of Leeds, Leeds, LS2 9JT, UK; E-Mail: [email protected] † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +44-113-343-1421; Fax: +44-113-343-2882. Received: 29 May 2013; in revised form: 12 July 2013 / Accepted: 22 July 2013 / Published: 20 August 2013 Abstract: Almost all protease families have been associated with plant development, particularly senescence, which is the final developmental stage of every organ before cell death.
    [Show full text]
  • Regulated Proteolytic Processing of Reelin Through Interplay of Tissue Plasminogen Activator (Tpa), ADAMTS-4, ADAMTS-5, and Their Modulators
    Regulated Proteolytic Processing of Reelin through Interplay of Tissue Plasminogen Activator (tPA), ADAMTS-4, ADAMTS-5, and Their Modulators Dimitrije Krstic, Myriam Rodriguez, Irene Knuesel* Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland Abstract The extracellular signaling protein Reelin, indispensable for proper neuronal migration and cortical layering during development, is also expressed in the adult brain where it modulates synaptic functions. It has been shown that proteolytic processing of Reelin decreases its signaling activity and promotes Reelin aggregation in vitro, and that proteolytic processing is affected in various neurological disorders, including Alzheimer’s disease (AD). However, neither the pathophysiological significance of dysregulated Reelin cleavage, nor the involved proteases and their modulators are known. Here we identified the serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, as Reelin cleaving enzymes. Moreover, we assessed the influence of several endogenous protease inhibitors, including tissue inhibitors of metalloproteinases (TIMPs), a-2-Macroglobulin, and multiple serpins, as well as matrix metalloproteinase 9 (MMP-9) on Reelin cleavage, and described their complex interplay in the regulation of this process. Finally, we could demonstrate that in the murine hippocampus, the expression levels and localization of Reelin proteases largely overlap with that of Reelin. While this pattern remained stable during normal aging, changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD. Citation: Krstic D, Rodriguez M, Knuesel I (2012) Regulated Proteolytic Processing of Reelin through Interplay of Tissue Plasminogen Activator (tPA), ADAMTS-4, ADAMTS-5, and Their Modulators. PLoS ONE 7(10): e47793.
    [Show full text]
  • Physiological Significance of Proteolytic Processing of Reelin
    www.nature.com/scientificreports OPEN Physiological signifcance of proteolytic processing of Reelin revealed by cleavage-resistant Reelin knock-in mice Eisuke Okugawa1,3, Himari Ogino1,3, Tomofumi Shigenobu1, Yuko Yamakage1, Hitomi Tsuiji1, Hisashi Oishi2, Takao Kohno1 & Mitsuharu Hattori1* Reelin is a secreted protein that plays versatile roles in neuronal development and function. The strength of Reelin signaling is regulated by proteolytic processing, but its importance in vivo is not yet fully understood. Here, we generated Reelin knock-in (PA-DV KI) mice in which the key cleavage site of Reelin was abolished by mutation. As expected, the cleavage of Reelin was severely abrogated in the cerebral cortex and hippocampus of PA-DV KI mice. The amount of Dab1, whose degradation is induced by Reelin signaling, decreased in these tissues, indicating that the signaling strength of Reelin was augmented. The brains of PA-DV KI mice were largely structurally normal, but unexpectedly, the hippocampal layer was disturbed. This phenotype was ameliorated in hemizygote PA-DV KI mice, indicating that excess Reelin signaling is detrimental to hippocampal layer formation. The neuronal dendrites of PA-DV KI mice had more branches and were elongated compared to wild-type mice. These results present the frst direct evidence of the physiological importance of Reelin cleavage. Reelin is a large secreted glycoprotein that regulates many important events in mammalian brain development1–3. It is also involved in synaptic plasticity and the modulation of higher brain functions1,4–8. At the cellular level, Reelin induces the clustering of apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein recep- tor (VLDLR), which is the prerequisite for the phosphorylation of the cytosolic adaptor protein Dab19–11.
    [Show full text]