DOCSLIB.ORG

Research Article in Silico Analysis of Stem Bromelain

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Research Article in Silico Analysis of Stem Bromelain INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES ISSN: 22775005 Research Article In Silico Analysis of Stem Bromelain GS. Sekhar*, P. Rajkeshwar and P. Anil Shambhunath Institute of Pharmacy, Jhalwa, Allahabad, Uttar Pradesh-211012, India. ABSTRACT Bromelain is a general name for a family of sulfhydryl-containing, proteolytic enzymes obtained from Ananas comosus. In this work we have performe Sequence analysis, Functional, Structural & Phylogenetic analysis and Prediction of protein structure of Stem Bromelain protein using different Bio-informatics tools and databases like as NCBI, BLAST, FASTA, Clustal W, Protein Data Bank etc. Sequence Similarity was search using BLAST against Homo sapiens protein database. Stem& Fruit Bromelain was extracted from Stem & Fruit of Pineapple plant which contains the enzymes Stem Bromelain (Cysteine endopeptidase ) and Fruit Bromelain (Aspartic endopeptidase), respectively. INTRODUCTION ovaries of many flowers more or less grown The pineapple (Ananas comosus) is placed in together into one mass. the Order Bromeliales and the Family Bromelain is a general name for a family of Bromeliaceae. It is a medium tall (1–1.5 m) sulfhydryl-containing, proteolytic enzymes herbaceous perennial plant with 30 or more obtained from Ananas comosus, the pineapple trough-shaped and pointed leaves 30–100 cm plant6-7. The primary component of Bromelain long, surrounding a thick stem. Pineapples is a sulfhydryl proteolytic fraction. It also are short stemmed, herbaceous plants having contains a peroxidase, acid phosphatase, basal rosettes of stiff, spiny leaves. The several protease inhibitors, and organically- flowers are clustered together on a short stalk bound calcium. It is made up of 212 amino that arises from the rosette of leaves. acids and the molecular weight is 33,000 D. Bioinformatics is the application of computer technology to the management of biological information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied to gene-based drug discovery and development17. The need for Bioinformatics capabilities has been precipitated by the Fig. 1: explosion of publicly available genomic information resulting from the Human Genome Project. The cluster of flowers resembles a pine cone, thus the name pineapple1-5. Leaves also grow MATERIALS AND METHODS from the top of the flower cluster. As the Bioinformatics tools and databases ovaries of the individual flowers on the stalk Stem Bromelain, the protein of interest was ripen, they swell up to form the pineapple fruit. analyzed using different Bioinformatics tools The pineapple fruit is considered a multiple and databases listed below: fruit because it consists of the enlarged S.No Tool / Database Application 1 NCBI Sequence retrieval 2 BLAST Sequence similarity 3 Clustal W Multiple Sequence Alignment 4 Clustal Distance Matrix Evolutionary distance 5 Protparam Primary Structure analysis 6 Hierarchial Neural Network Secondary Structure analysis 7 CPH, HHPred Tertiary Structure analysis 8 Protein Data Bank (PDB) 3D-structure 9 Rasmol 3D-structure visualization Vol. 2 (2) Apr-Jun 2013 www.ijpcsonline.com 992 INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES ISSN: 22775005 1) Sequence analysis Sequence Similarity Analysis For sequence analysis we have retrieve the Sequence Similarity was search using sequence Stem Bromelain form NCBI in BLAST14 against Homo sapiens protein FASTA format. database. In bioinformatics, Basic Local Alignment Aminoacid sequence of Stem Bromelain Search Tool, or BLAST, is an algorithm for >gi|115139|sp|P14518.1|BROM2_ANACO comparing primary biological sequence Stem bromelain information, such as the amino-acid AVPQSIDWRDYGAVTSVKNQNPCGACWAF sequences of different proteins or the AAIATVESIYKIKKGILEPLSEQQVLDCAKGYG nucleotides of DNA sequences. A BLAST CKGGWEFRAFEFIISNKGVASGAIYPYKAAK search enables a researcher to compare a GTCKTDGVPNSAYITGYARVPRNNESSMMY query sequence with a library or database of AVSKQPITVAVDANANFQYYKSGVFNGPCG sequences, and identify library sequences that TSLNHAVTAIGYGQDSIIYPKKWGAKWGEAG resemble the query sequence above a certain YIRMARDVSSSSGICGIAIDPLYPTLEE threshold. Length: 212 aa I have searched for the protein sequences of Homo sapiens showing maximum similarity Function with the query sequence i.e. Stem bromelain, Peptidase C1A subfamily; (composed of by using the Sequence Similarity search tool cysteine peptidases (CPs) similar to papain, “Basic Local Alignment Search Tool” (BLAST). including the mammalian CPs (cathepsins B, I have performed Protein-Protein BLAST and C, F, H, L, K, O, S, V, X and W). Papain is an selected 4 sequences showing maximum endopeptidase with specific substrate similarity depending on the parameters viz., preferences, primarily for bulky hydrophobic or Score, e-value, Identities, Positives & Gaps. aromatic residues at the S2 subsite, a They were represented below : hydrophobic pocket in papain that >gb|AAH02642.1| Cathepsin S [Homo accommodates the P2 sidechain of the sapiens] substrate (the second residue away from the emb|CAG46477.1| CTSS [Homo scissile bond). Most members of the papain sapiens] subfamily are endopeptidases. Some Length=331 exceptions to this rule can be explained by GENE ID: 1520 CTSS | cathepsin S [Homo specific details of the catalytic domains like the sapiens] occluding loop in cathepsin B which confers an Score = 101 bits (226), Expect = 2e-21, additional carboxydipeptidyl activity and the Method: Compositional matrix adjust. mini-chain of cathepsin H resulting in an N- Identities = 59/147 (40%), Positives = 84/147 terminal exopeptidase activity. (57%), Gaps = 10/147 (6%) Papain-like CPs have different functions in various organisms15-16. Plant CPs are used to FASTA format mobilize storage proteins in seeds. Parasitic >gi|12803615|gb|AAH02642.1| Cathepsin S CPs act extracellularly to help invade tissues [Homo sapiens] and cells, to hatch or to evade the host MKRLVCVLLVCSSAVAQLHKDPTLDHHWHL immune system. Mammalian CPs are primarily WKKTYGKQYKEKNEEAVRRLIWEKNLKFVM lysosomal enzymes with the exception of LHNLEHSMGMHSYDLGMNHLGDMTSEEVM cathepsin W, which is retained in the SLMSSLRVPSQWQRNITYKSNPNWILPDSV endoplasmic reticulum. They are responsible DWREKGCVTEVKYQGSCGACWAFSAVGAL for protein degradation in the lysosome. EAQLKLKTGKLVSLSAQNLVDCSTEKYGNK Papain-like CPs are synthesized as inactive GCNGGFMTTAFQYIIDNKGIDSDASYPYKAM proenzymes with N-terminal propeptide DQKCQYDSKYRAATCSKYTELPYGREDVLK regions, which are removed upon activation. In EAVANKGPVSVGVDARHPSFFLYRSGVYYE addition to its inhibitory role, the propeptide is PSCTQNVNHGVLVVGYGDLNGKEYWLVKN required for proper folding of the newly SWGHNFGEEGYIRMARNKGNHCGIASFPSY synthesized enzyme and its stabilization in PEI. denaturing pH conditions. Residues within the propeptide region also play a role in the Function transport of the proenzyme to lysosomes or Cathepsin propeptide inhibitor domain (I29). acidified vesicles. Also included in this This domain is found at the N-terminus of subfamily are proteins classified as non- some C1 peptidases such as Cathepsin L peptidase homologs, which lack peptidase where it acts as a propeptide. There are also a activity or have missing active site residues. number of proteins that are composed solely of multiple copies of this domain such as the Vol. 2 (2) Apr-Jun 2013 www.ijpcsonline.com 993 INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES ISSN: 22775005 peptidase inhibitor salarin. This family is GENE ID: 1512 CTSH | cathepsin H [Homo classified as I29 by MEROPS18-20. sapiens] Peptidase C1A subfamily; composed of Score = 136 bits (308), Expect = 6e-32, cysteine peptidases (CPs) similar to papain, Method: Compositional matrix adjust. including the mammalian CPs (cathepsins B, Identities = 77/219 (35%), Positives = 118/219 C, F, H, L, K, O, S, V, X and W). Papain is an (53%), Gaps = 17/219 (7%). endopeptidase with specific substrate preferences, primarily for bulky hydrophobic or FASTA format aromatic residues at the S2 subsite, a >gi|16506813|gb|AAL23961.1|AF426247_1 hydrophobic pocket in papain that cathepsin H [Homo sapiens] accommodates the P2 sidechain of the MWATLPLLCAGAWLLGVPVCGAAELCVNSL substrate (the second residue away from the EKFHFKSWMSKHRKTYSTEEYHHRLQTFAS scissile bond). Most members of the papain NWRKINAHNNGNHTFKMALNQFSDMSFAEI subfamily are endopeptidases. Some KHKYLWSEPQNCSATKSNYLRGTGPYPPSV exceptions to this rule can be explained by DWRKKGNFVSPVKNQGACGSCWTFSTTGA specific details of the catalytic domains like the LESAIAIATGKMLSLAEQQLVDCAQDFNNYG occluding loop in cathepsin B which confers an CQGGLPSQAFEYILYNKGIMGEDTYPYQGK additional carboxydipeptidyl activity and the DGYCKFQPGKAIGFVKDVANITIYDEEAMVE mini-chain of cathepsin H resulting in an N- AVALYNPVSFAFEVTQDFMMYRTGIYSSTSC terminal exopeptidase activity. Papain-like HKTPDKVNHAVLAVGYGEKNGIPYWIVKNS CPs have different functions in various WGPQWGMNGYFLIERGKNMCGLAACASYP organisms. Plant CPs are used to mobilize IPLV storage proteins in seeds. Parasitic CPs act extracellularly to help invade tissues and cells, Inference to hatch or to evade the host immune system. The Query Sequence i.e. Stem Bromelain Mammalian CPs are primarily lysosomal protein sequence is showing maximum enzymes with the exception of cathepsin W, Sequence and functional similarity with which is retained in the endoplasmic reticulum. different types of Cathepsins of Homo sapiens. They are responsible for protein degradation in The Query sequence and
Load more

Recommended publications
  • Enzymes Handling/Processing
    Enzymes Handling/Processing 1 Identification of Petitioned Substance 2 3 This Technical Report addresses enzymes used in used in food processing (handling), which are 4 traditionally derived from various biological sources that include microorganisms (i.e., fungi and 5 bacteria), plants, and animals. Approximately 19 enzyme types are used in organic food processing, from 6 at least 72 different sources (e.g., strains of bacteria) (ETA, 2004). In this Technical Report, information is 7 provided about animal, microbial, and plant-derived enzymes generally, and more detailed information 8 is presented for at least one model enzyme in each group. 9 10 Enzymes Derived from Animal Sources: 11 Commonly used animal-derived enzymes include animal lipase, bovine liver catalase, egg white 12 lysozyme, pancreatin, pepsin, rennet, and trypsin. The model enzyme is rennet. Additional details are 13 also provided for egg white lysozyme. 14 15 Chemical Name: Trade Name: 16 Rennet (animal-derived) Rennet 17 18 Other Names: CAS Number: 19 Bovine rennet 9001-98-3 20 Rennin 25 21 Chymosin 26 Other Codes: 22 Prorennin 27 Enzyme Commission number: 3.4.23.4 23 Rennase 28 24 29 30 31 Chemical Name: CAS Number: 32 Peptidoglycan N-acetylmuramoylhydrolase 9001-63-2 33 34 Other Name: Other Codes: 35 Muramidase Enzyme Commission number: 3.2.1.17 36 37 Trade Name: 38 Egg white lysozyme 39 40 Enzymes Derived from Plant Sources: 41 Commonly used plant-derived enzymes include bromelain, papain, chinitase, plant-derived phytases, and 42 ficin. The model enzyme is bromelain.
    [Show full text]
  • Biochemistry and the Genomic Revolution 1.1
    Dedication About the authors Preface Tools and Techniques Clinical Applications Molecular Evolution Supplements Supporting Biochemistry, Fifth Edition Acknowledgments I. The Molecular Design of Life 1. Prelude: Biochemistry and the Genomic Revolution 1.1. DNA Illustrates the Relation between Form and Function 1.2. Biochemical Unity Underlies Biological Diversity 1.3. Chemical Bonds in Biochemistry 1.4. Biochemistry and Human Biology Appendix: Depicting Molecular Structures 2. Biochemical Evolution 2.1. Key Organic Molecules Are Used by Living Systems 2.2. Evolution Requires Reproduction, Variation, and Selective Pressure 2.3. Energy Transformations Are Necessary to Sustain Living Systems 2.4. Cells Can Respond to Changes in Their Environments Summary Problems Selected Readings 3. Protein Structure and Function 3.1. Proteins Are Built from a Repertoire of 20 Amino Acids 3.2. Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains 3.3. Secondary Structure: Polypeptide Chains Can Fold Into Regular Structures Such as the Alpha Helix, the Beta Sheet, and Turns and Loops 3.4. Tertiary Structure: Water-Soluble Proteins Fold Into Compact Structures with Nonpolar Cores 3.5. Quaternary Structure: Polypeptide Chains Can Assemble Into Multisubunit Structures 3.6. The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure Summary Appendix: Acid-Base Concepts Problems Selected Readings 4. Exploring Proteins 4.1. The Purification of Proteins Is an Essential First Step in Understanding Their Function 4.2. Amino Acid Sequences Can Be Determined by Automated Edman Degradation 4.3. Immunology Provides Important Techniques with Which to Investigate Proteins 4.4. Peptides Can Be Synthesized by Automated Solid-Phase Methods 4.5.
    [Show full text]
  • Alimentary Tract Proteinases of the Southern Corn
    Durham E-Theses Alimentary tract proteinases of the Southern corn rootworm (Diabrotica undecimpunctata howardi) and the potential of potato Kunitz proteinase inhibitors for larval control. Macgregor, James Mylne How to cite: Macgregor, James Mylne (2001) Alimentary tract proteinases of the Southern corn rootworm (Diabrotica undecimpunctata howardi) and the potential of potato Kunitz proteinase inhibitors for larval control., Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/3808/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk 2 Alimentary tract proteinases of the Southern corn rootworm (Diabrotica undecimpunctata howardi) and the potential of potato Kunitz proteinase inhibitors for larval control. The copyright of this thesis rests with the author. No quotation from it should be published without his prior written consent and information derived from it should be acknowledged. A thesis submitted by James Mylne Macgregor B.Sc.
    [Show full text]
  • Serine Proteases with Altered Sensitivity to Activity-Modulating
    (19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants.
    [Show full text]
  • Molecular Insights Into Bromelain Application in Industry and Health Care
    Biosc.Biotech.Res.Comm. Special Issue Vol 13 No 15 (2020) Pp-36-46 Molecular Insights into Bromelain Application in Industry and Health Care Sushma S. Murthy and T. Bala Narsaiah 1Research Scholar, Department of Chemical Engineering, JNTUA College of Engineering, Ananthapuram-515002, Andhra Pradesh, India 2Department of Chemical Engineering, JNTUA College of Engineering, Ananthapuram-515002, Andhra Pradesh, India ABSTRACT Bromelain is a cysteine protease derived from the stem and fruit of the pineapple. It has a significant role in pharmacological and clinical applications. Studies have shown Bromelain to be a potent photoactive compound that has a wide application in industry. It has also been shown to be effective in treatment of cancer, inflammation, and allergies. It has a distinct immunomodulatory activity which forms an important strategy in its utilization as a therapeutic agent. Bromelain plays a significant role at molecular level by regulating the expression of proteins that are potential therapeutic targets. Bromelain is used extensively worldwide as an herbal medicine as it promises good efficacy and has no side effects. This paper reviews the general characteristics of Bromelain, its separation process, and its use in industries and healthcare as a therapeutic agent. The present review identifies that there is lack of knowledge pertaining to the mode of action of Bromelain in inhibiting transcriptional factors and in controlling cancer. An in-detail analysis in this area might help in expanding the therapeutic scope of Bromelain. KEY WORDS: BROMELAIN, CANCER, PHARMacOLOGICAL actiVITY, SEpaRatiON, TRANSCRIPTION FactORS. INTRODUCTION because of its wide benefits to the human system. The stem part of the plant, which is inexpensive and is usually The Bromelain protease is isolated from the stem and discarded, has a high concentration of bromelain and fruit of Pineapple (Ananas comosus,).
    [Show full text]
  • Inhibition of Mitochondrial Complex II in Neuronal Cells Triggers Unique
    www.nature.com/scientificreports OPEN Inhibition of mitochondrial complex II in neuronal cells triggers unique pathways culminating in autophagy with implications for neurodegeneration Sathyanarayanan Ranganayaki1, Neema Jamshidi2, Mohamad Aiyaz3, Santhosh‑Kumar Rashmi4, Narayanappa Gayathri4, Pulleri Kandi Harsha5, Balasundaram Padmanabhan6 & Muchukunte Mukunda Srinivas Bharath7* Mitochondrial dysfunction and neurodegeneration underlie movement disorders such as Parkinson’s disease, Huntington’s disease and Manganism among others. As a corollary, inhibition of mitochondrial complex I (CI) and complex II (CII) by toxins 1‑methyl‑4‑phenylpyridinium (MPP+) and 3‑nitropropionic acid (3‑NPA) respectively, induced degenerative changes noted in such neurodegenerative diseases. We aimed to unravel the down‑stream pathways associated with CII inhibition and compared with CI inhibition and the Manganese (Mn) neurotoxicity. Genome‑wide transcriptomics of N27 neuronal cells exposed to 3‑NPA, compared with MPP+ and Mn revealed varied transcriptomic profle. Along with mitochondrial and synaptic pathways, Autophagy was the predominant pathway diferentially regulated in the 3‑NPA model with implications for neuronal survival. This pathway was unique to 3‑NPA, as substantiated by in silico modelling of the three toxins. Morphological and biochemical validation of autophagy markers in the cell model of 3‑NPA revealed incomplete autophagy mediated by mechanistic Target of Rapamycin Complex 2 (mTORC2) pathway. Interestingly, Brain Derived Neurotrophic Factor
    [Show full text]
  • Untersuchung Zur Selektivität Der Hemmung Von Cathepsin L-Ähnlichen Cysteinproteasen Durch Die Dazugehörigen Propeptide
    Untersuchung zur Selektivität der Hemmung von Cathepsin L-ähnlichen Cysteinproteasen durch die dazugehörigen Propeptide Dissertation zur Erlangung des akademischen Grades doctor medicinae dentariae (Dr. med. dent.) vorgelegt dem Rat der Medizinischen Fakultät der Friedrich-Schiller-Universität Jena von Yvonne Benedix, geboren am 05. Februar 1979 in Karl-Marx-Stadt Gutachter 1 Gutachter 2 Gutachter 3 Tag der öffentlichen Verteidigung Inhaltsverzeichnis 3 Abkürzungsverzeichnis 5 Zusammenfassung 7 1. Einleitung 9 2. Materialien und Methodik 16 2.1. Materialien 16 2.1.1. Antibiotika, Chemikalien, Enzyme, Standards und Substrate 16 2.1.2. Kits zur Bearbeitung von DNA 17 2.1.3. Verwendete Vektoren und Bakterienstämme 17 2.1.4. Geräte 18 2.1.5. Spezielle Computerprogramme 19 2.2. Molekularbiologische Methoden 19 2.2.1. Amplifizierung der Proregionen von Cathepsin H und L 19 mittels PCR 2.2.2. DNA-Trennung im Agarosegel und Extraktion 21 2.2.3. Klonierung, Ligation, Transformation und DNA-Isolierung 21 2.2.4. DNA-Seqzenzanalyse 25 2.3. Proteinchemische Methoden 26 2.3.1. Expression und Reinigung der rekombinanten Propeptide 26 2.3.2. Reinigung der Einschlusskörperchen durch Saccharose- Dichtegradientenzentrifugation 27 2.3.3. Endreinigung des Propeptids durch Gelfiltration 28 2.3.4. Charakterisierung der rekombinanten Propeptide 29 2.3.5. Massenspektrometrie durch MALDI-TOF 31 2.4. Kinetische Messung 31 2.4.1. Testdurchführung 31 2.4.2. Bestimmung des KM-Wertes 33 2.4.3. Bestimmung der Inhibitionskonstanten Ki und koff 34 3. Ergebnisse 37 3.1. Herstellung der Propeptide von Cathepsin H (kurz), Cathepsin H (lang) und Cathepsin L 37 3.1.1.
    [Show full text]
  • Reticulum Mainly Localized in the Endoplasmic Predominantly
    Human Cathepsin W, a Cysteine Protease Predominantly Expressed in NK Cells, Is Mainly Localized in the Endoplasmic Reticulum This information is current as of September 24, 2021. Thomas Wex, Frank Bühling, Heike Wex, Dagmar Günther, Peter Malfertheiner, Ekkehard Weber and Dieter Brömme J Immunol 2001; 167:2172-2178; ; doi: 10.4049/jimmunol.167.4.2172 http://www.jimmunol.org/content/167/4/2172 Downloaded from References This article cites 44 articles, 18 of which you can access for free at: http://www.jimmunol.org/content/167/4/2172.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Human Cathepsin W, a Cysteine Protease Predominantly Expressed in NK Cells, Is Mainly Localized in the Endoplasmic Reticulum1 Thomas Wex,2,3*† Frank Bu¨hling,2§ Heike Wex,*‡ Dagmar Gu¨nther,¶ Peter Malfertheiner,† Ekkehard Weber,¶ and Dieter Bro¨mme3* Human cathepsin W (also called lymphopain) is a recently described papain-like cysteine protease of unknown function whose gene expression was found to be restricted to cytotoxic cells.
    [Show full text]
  • Cysteine Cathepsins: from Structure, Function and Regulation to New Frontiers☆
    Biochimica et Biophysica Acta 1824 (2012) 68–88 Contents lists available at SciVerse ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbapap Review Cysteine cathepsins: From structure, function and regulation to new frontiers☆ Vito Turk a,b,⁎⁎, Veronika Stoka a, Olga Vasiljeva a, Miha Renko a, Tao Sun a,1, Boris Turk a,b,c,Dušan Turk a,b,⁎ a Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia b Center of Excellence CIPKEBIP, Ljubljana, Slovenia c Center of Excellence NIN, Ljubljana, Slovenia article info abstract Article history: It is more than 50 years since the lysosome was discovered. Since then its hydrolytic machinery, including Received 16 August 2011 proteases and other hydrolases, has been fairly well identified and characterized. Among these are the cyste- Received in revised form 3 October 2011 ine cathepsins, members of the family of papain-like cysteine proteases. They have unique reactive-site prop- Accepted 4 October 2011 erties and an uneven tissue-specific expression pattern. In living organisms their activity is a delicate balance Available online 12 October 2011 of expression, targeting, zymogen activation, inhibition by protein inhibitors and degradation. The specificity of their substrate binding sites, small-molecule inhibitor repertoire and crystal structures are providing new Keywords: fi Cysteine cathepsin tools for research and development. Their unique reactive-site properties have made it possible to con ne the Protein inhibitor targets simply by the use of appropriate reactive groups. The epoxysuccinyls still dominate the field, but now Cystatin nitriles seem to be the most appropriate “warhead”.
    [Show full text]
  • Cathepsins and Their Involvement in Immune Responses
    Review article: Medical intelligence | Published 20 July 2010, doi:10.4414/smw.2010.13042 Cite this as: Swiss Med Wkly. 2010;140:w13042 Cathepsins and their involvement in immune responses Sébastien Conus, Hans-Uwe Simon Institute of Pharmacology, University of Bern, Bern, Switzerland Correspondence to: cleaving proteases (= caspases) which cleave a wide range Sébastien Conus Ph.D. of cellular substrates [5]. Institute of Pharmacology Besides caspases, cathepsins have recently been shown University of Bern to be associated with cell death regulation [6–12] and vari- Friedbühlstrasse 49 3010 Bern ous other physiological and pathological processes, such as Switzerland maturation of the MHC class II complex, bone remodel- [email protected] ling, keratinocyte differentiation, tumour progression and metastasis, rheumatoid arthritis and osteoarthritis, as well Summary as atherosclerosis [13, 14] (table 1). Thus, cathepsins ap- pear to play a significant role in immune responses. In this The immune system is composed of an enormous variety of review we discuss recent advances addressing the role of cells and molecules that generate a collective and coordin- lysosomal proteases in the diverse aspects of the immune ated response on exposure to foreign antigens, called the response, and also the involvement of cathepsins in the immune response. Within the immune response, endo-lyso- pathogenesis of diseases in which these proteases seem not somal proteases play a key role. In this review we cover to be properly under control. specific roles of cathepsins in innate and adaptive immu- nity, as well as their implication in the pathogenesis of sev- The cathepsin family eral diseases. Lysosomes are membrane-bound organelles which repres- Key words: adaptive and innate immunity; apoptosis; ent the main degradative compartment in eukaryotic cells.
    [Show full text]
  • Role of Systemic Enzymes in Infections
    Article ID: WMC002495 2046-1690 Role of Systemic Enzymes in Infections Corresponding Author: Dr. Sukhbir Shahid, Consultant Pediatrician, Pediatrics - India Submitting Author: Dr. Sukhbir Shahid, Consultant Pediatrician, Pediatrics - India Article ID: WMC002495 Article Type: Review articles Submitted on:22-Nov-2011, 08:16:56 AM GMT Published on: 22-Nov-2011, 02:34:00 PM GMT Article URL: http://www.webmedcentral.com/article_view/2495 Subject Categories:COMPLEMENTARY MEDICINE Keywords:Enzymes, Systemic enzymes, Infections, Sepsis, Proteolytic, Supplementary How to cite the article:Shahid S . Role of Systemic Enzymes in Infections . WebmedCentral COMPLEMENTARY MEDICINE 2011;2(11):WMC002495 Source(s) of Funding: None Competing Interests: None WebmedCentral > Review articles Page 1 of 13 WMC002495 Downloaded from http://www.webmedcentral.com on 23-Dec-2011, 07:57:46 AM Role of Systemic Enzymes in Infections Author(s): Shahid S Abstract infections[4]. The ‘battle’ between the host’s immunity and organism leads to a lot of ‘molecular’morbidity and mortality. Anti-infective agents do help but at times benefit is marginal. These agents may sometimes Enzymes are complex macromolecules of amino-acids worsen the situation through release of immune which bio-catalyse various body processes. Adequate complexes and dead bacilli into the blood stream. concentrations of enzymes are essential for optimal They also fail to reverse the hemodynamic instability functioning of the immune system. During infections, and immune paralysis characteristic of these body’s enzymatic system is attacked and hence the infections[4]. Supplementation with drugs targeted immune system is also likely to derange. This may be against this ‘choatic’ or ‘dysfunctional’ immune detrimental for the host’s well-being and existence.
    [Show full text]
  • Concentrate of Proteolytic Enzymes Enriched in Bromelain
    20 September 2012 EMA/648483/2012 Committee for Medicinal Products for Human Use (CHMP) Assessment report NexoBrid Concentrate of proteolytic enzymes enriched in bromelain Procedure No. EMEA/H/C/002246 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2012. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 5 1.1. Submission of the dossier.................................................................................... 5 1.2. Steps taken for the assessment of the product ....................................................... 6 2. Scientific discussion ................................................................................ 7 2.1. Introduction ...................................................................................................... 7 2.2. Quality aspects .................................................................................................. 9 2.3. Non-clinical aspects .......................................................................................... 20 2.4. Clinical aspects ................................................................................................ 29 2.5.
    [Show full text]