Crystal Structure of Cathepsin X: a Flip–Flop of the Ring of His23
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Supplementary Data
Supplementary Data for Quantitative Changes in the Mitochondrial Proteome from Subjects with Mild Cognitive Impairment, Early Stage and Late Stage Alzheimer’s disease Table 1 - 112 unique, non-redundant proteins identified and quantified in at least two of the three analytical replicates for all three disease stages. Table 2 - MCI mitochondrial samples, Protein Summary Table 3 - MCI mitochondrial samples, Experiment 1 Table 4 - MCI mitochondrial samples, Experiment 2 Table 5 - MCI mitochondrial samples, Experiment 3 Table 6 - EAD Mitochondrial Study, Protein Summary Table 7 - EAD Mitochondrial Study, Experiment 1 Table 8 - EAD Mitochondrial Study, Experiment 2 Table 9 - EAD Mitochondrial Study, Experiment 3 Table 10 - LAD Mitochondrial Study, Protein Summary Table 11 - LAD Mitochondrial Study, Experiment 1 Table 12 - LAD Mitochondrial Study, Experiment 2 Table 13 - LAD Mitochondrial Study, Experiment 3 Supplemental Table 1. 112 unique, non-redundant proteins identified and quantified in at least two of the three analytical replicates for all three disease stages. Description Data MCI EAD LAD AATM_HUMAN (P00505) Aspartate aminotransferase, mitochondrial precursor (EC Mean 1.43 1.70 1.31 2.6.1.1) (Transaminase A) (Glutamate oxaloacetate transaminase 2) [MASS=47475] SEM 0.07 0.09 0.09 Count 3.00 3.00 3.00 ACON_HUMAN (Q99798) Aconitate hydratase, mitochondrial precursor (EC 4.2.1.3) Mean 1.24 1.61 1.19 (Citrate hydro-lyase) (Aconitase) [MASS=85425] SEM 0.05 0.17 0.18 Count 3.00 2.00 3.00 ACPM_HUMAN (O14561) Acyl carrier protein, mitochondrial -
The International Journal of Biochemistry & Cell Biology
The International Journal of Biochemistry & Cell Biology 41 (2009) 1685–1696 Contents lists available at ScienceDirect The International Journal of Biochemistry & Cell Biology journal homepage: www.elsevier.com/locate/biocel Cathepsin X cleaves the C-terminal dipeptide of alpha- and gamma-enolase and impairs survival and neuritogenesis of neuronal cells Natasaˇ Obermajer a,b,∗, Bojan Doljak a, Polona Jamnik c,Ursaˇ Pecarˇ Fonovic´ a, Janko Kos a,b a University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia b Jozef Stefan Institute, Department of Biotechnology, Jamova 39, 1000 Ljubljana, Slovenia c University of Ljubljana, Biotechnical Faculty, Jamnikarjeva 101, 1000 Ljubljana, Slovenia article info abstract Article history: The cysteine carboxypeptidase cathepsin X has been recognized as an important player in degenerative Received 22 January 2009 processes during normal aging and in pathological conditions. In this study we identify isozymes alpha- Received in revised form 17 February 2009 and gamma-enolases as targets for cathepsin X. Cathepsin X sequentially cleaves C-terminal amino acids Accepted 18 February 2009 of both isozymes, abolishing their neurotrophic activity. Neuronal cell survival and neuritogenesis are, Available online 6 March 2009 in this way, regulated, as shown on pheochromocytoma cell line PC12. Inhibition of cathepsin X activity increases generation of plasmin, essential for neuronal differentiation and changes the length distribution Keywords: of neurites, especially in the early phase of neurite outgrowth. Moreover, cathepsin X inhibition increases Cathepsin X Enolase neuronal survival and reduces serum deprivation induced apoptosis, particularly in the absence of nerve Neuritogenesis growth factor. On the other hand, the proliferation of cells is decreased, indicating induction of differ- Neuronal cell survival entiation. -
Helical Domain That Prevents Access to the Substrate-Binding Cleft
View metadata, citation and similar papers at core.ac.uk brought to you by CORE Researchprovided Article by Elsevier1193 - Publisher Connector The prosequence of procaricain forms an a-helical domain that prevents access to the substrate-binding cleft Matthew R Groves, Mark AJ Taylor, Mandy Scott, Nicola J Cummings Richard W Pickersgill* and John A Jenkins* Background: Cysteine proteases are involved in a variety of cellular processes Address: Department of Food Macromolecular including cartilage degradation in arthritis, the progression of Alzheimer’s Science, Institute of Food Research, Earley Gate, disease and cancer invasion: these enzymes are therefore of immense biological Whiteknights Road, Reading, RG6 6BZ, UK. importance. Caricain is the most basic of the cysteine proteases found in the *Corresponding authors. latex of Carica papaya. It is a member of the papain superfamily and is E-mail: [email protected] homologous to other plant and animal cysteine proteases. Caricain is naturally [email protected] expressed as an inactive zymogen called procaricain. The inactive form of the Key words: caricain, cysteine protease, density protease contains an inhibitory proregion which consists of an additional 106 modification, X-ray structure, zymogen N-terminal amino acids; the proregion is removed upon activation. Received: 25 June 1996 Results: The crystal structure of procaricain has been refined to 3.2 Å Revisions requested: 23 July 1996 Revisions received: 12 August 1996 resolution; the final model consists of three non-crystallographically related Accepted: 28 August 1996 molecules. The proregion of caricain forms a separate globular domain which binds to the C-terminal domain of mature caricain. -
Data Sheet Cathepsin V Inhibitor Screening Assay Kit Catalog #79589 Size: 96 Reactions
6405 Mira Mesa Blvd Ste. 100 San Diego, CA 92121 Tel: 1.858.202.1401 Fax: 1.858.481.8694 Email: [email protected] Data Sheet Cathepsin V Inhibitor Screening Assay Kit Catalog #79589 Size: 96 reactions BACKGROUND: Cathepsin V, also called Cathepsin L2, is a lysosomal cysteine endopeptidase with high sequence homology to cathepsin L and other members of the papain superfamily of cysteine proteinases. Its expression is regulated in a tissue-specific manner and is high in thymus, testis and cornea. Expression analysis of cathepsin V in human tumors revealed widespread expression in colorectal and breast carcinomas, suggesting a possible role in tumor processes. DESCRIPTION: The Cathepsin V Inhibitor Screening Assay Kit is designed to measure the protease activity of Cathepsin V for screening and profiling applications. The Cathepsin V assay kit comes in a convenient 96-well format, with purified Cathepsin V, its fluorogenic substrate, and Cathepsin buffer for 100 enzyme reactions. In addition, the kit includes the cathepsin inhibitor E- 64 for use as a control inhibitor. COMPONENTS: Catalog # Component Amount Storage 80009 Cathepsin V 10 µg -80 °C Fluorogenic Cathepsin Avoid 80349 Substrate 1 (5 mM) 10 µl -20 °C multiple *4X Cathepsin buffer 2 ml -20 °C freeze/thaw E-64 (1 mM) 10 µl -20 °C cycles! 96-well black microplate * Add 120 µl of 0.5 M DTT before use. MATERIALS OR INSTRUMENTS REQUIRED BUT NOT SUPPLIED: 0.5 M DTT in aqueous solution Adjustable micropipettor and sterile tips Fluorescent microplate reader APPLICATIONS: Great for studying enzyme kinetics and screening small molecular inhibitors for drug discovery and HTS applications. -
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. -
The Use of Fluorescence Resonance Energy Transfer (FRET) Peptides for Measurement of Clinically Important Proteolytic Enzymes
“main” — 2009/7/27 — 13:55 — page 381 — #1 Anais da Academia Brasileira de Ciências (2009) 81(3): 381-392 (Annals of the Brazilian Academy of Sciences) ISSN 0001-3765 www.scielo.br/aabc The use of Fluorescence Resonance Energy Transfer (FRET) peptides for measurement of clinically important proteolytic enzymes ADRIANA K. CARMONA, MARIA APARECIDA JULIANO and LUIZ JULIANO Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo Rua 3 de Maio, 100, 04044-020 São Paulo, SP, Brasil Manuscript received on June 30, 2008; accepted for publication on September 9, 2008; contributed by LUIZ JULIANO* ABSTRACT Proteolytic enzymes have a fundamental role in many biological processes and are associated with multiple patholog- ical conditions. Therefore, targeting these enzymes may be important for a better understanding of their function and development of therapeutic inhibitors. Fluorescence Resonance Energy Transfer (FRET) peptides are convenient tools for the study of peptidases specificity as they allow monitoring of the reaction on a continuous basis, providing arapid method for the determination of enzymatic activity. Hydrolysis of a peptide bond between the donor/acceptor pair generates fluorescence that permits the measurement of the activity of nanomolar concentrations of the enzyme.The assays can be performed directly in a cuvette of the fluorimeter or adapted for determinations in a 96-well fluorescence plate reader. The synthesis of FRET peptides containing ortho-aminobenzoic acid (Abz) as fluorescent group and 2,4-dinitrophenyl (Dnp) or N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) as quencher was optimized by our group and became an important line of research at the Department of Biophysics of the Federal University of São Paulo. -
Felipe Jun Fuzita Molecular Physiology of Digestion In
FELIPE JUN FUZITA MOLECULAR PHYSIOLOGY OF DIGESTION IN ARACHNIDA: FUNCTIONAL AND COMPARATIVE-EVOLUTIONARY APPROACHES Thesis presented to the Programa de Pós-Graduação Interunidades em Biotecnologia USP/Instituto Butantan/IPT, to obtain the Title of Doctor in Biotechnology. São Paulo 2014 FELIPE JUN FUZITA MOLECULAR PHYSIOLOGY OF DIGESTION IN ARACHNIDA: FUNCTIONAL AND COMPARATIVE-EVOLUTIONARY APPROACHES Thesis presented to the Programa de Pós-Graduação Interunidades em Biotecnologia USP/Instituto Butantan/IPT, to obtain the Title of Doctor in Biotechnology. Concentration area: Biotechnology Advisor: Dr. Adriana Rios Lopes Rocha Corrected version. The original electronic version is available either in the library of the Institute of Biomedical Sciences and in the Digital Library of Theses and Dissertations of the University of Sao Paulo (BDTD). São Paulo 2014 DADOS DE CATALOGAÇÃO NA PUBLICAÇÃO (CIP) Serviço de Biblioteca e Informação Biomédica do Instituto de Ciências Biomédicas da Universidade de São Paulo © reprodução total Fuzita, Felipe Jun. Molecular physiology of digestion in Arachnida: functional and comparative-evolutionary approaches / Felipe Jun Fuzita. -- São Paulo, 2014. Orientador: Profa. Dra. Adriana Rios Lopes Rocha. Tese (Doutorado) – Universidade de São Paulo. Instituto de Ciências Biomédicas. Programa de Pós-Graduação Interunidades em Biotecnologia USP/IPT/Instituto Butantan. Área de concentração: Biotecnologia. Linha de pesquisa: Bioquímica, biologia molecular, espectrometria de massa. Versão do título para o português: Fisiologia molecular da digestão em Arachnida: abordagens funcional e comparativo-evolutiva. 1. Digestão 2. Aranha 3. Escorpião 4. Enzimologia 5. Proteoma 6. Transcriptoma I. Rocha, Profa. Dra. Adriana Rios Lopes I. Universidade de São Paulo. Instituto de Ciências Biomédicas. Programa de Pós-Graduação Interunidades em Biotecnologia USP/IPT/Instituto Butantan III. -
Food Proteins Are a Potential Resource for Mining
Hypothesis Article: Food Proteins are a Potential Resource for Mining Cathepsin L Inhibitory Drugs to Combat SARS-CoV-2 Ashkan Madadlou1 1Wageningen Universiteit en Research July 20, 2020 Abstract The entry of SARS-CoV-2 into host cells proceeds by a two-step proteolysis process, which involves the lysosomal peptidase cathepsin L. Inhibition of cathepsin L is therefore considered an effective method to prevent the virus internalization. Analysis from the perspective of structure-functionality elucidates that cathepsin L inhibitory proteins/peptides found in food share specific features: multiple disulfide crosslinks (buried in protein core), lack or low contents of a-helix structures (small helices), and high surface hydrophobicity. Lactoferrin can inhibit cathepsin L, but not cathepsins B and H. This selective inhibition might be useful in fine targeting of cathepsin L. Molecular docking indicated that only the carboxyl-terminal lobe of lactoferrin interacts with cathepsin L and that the active site cleft of cathepsin L is heavily superposed by lactoferrin. Food protein-derived peptides might also show cathepsin L inhibitory activity. Abstract The entry of SARS-CoV-2 into host cells proceeds by a two-step proteolysis process, which involves the lyso- somal peptidase cathepsin L. Inhibition of cathepsin L is therefore considered an effective method to prevent the virus internalization. Analysis from the perspective of structure-functionality elucidates that cathepsin L inhibitory proteins/peptides found in food share specific features: multiple disulfide crosslinks (buried in protein core), lack or low contents of a-helix structures (small helices), and high surface hydrophobicity. Lactoferrin can inhibit cathepsin L, but not cathepsins B and H. -
Cells T+ HLA-DR + Processing in Human CD4 Cathepsin S
Cathepsin S Regulates Class II MHC Processing in Human CD4 + HLA-DR+ T Cells This information is current as Cristina Maria Costantino, Hidde L. Ploegh and David A. of September 26, 2021. Hafler J Immunol 2009; 183:945-952; Prepublished online 24 June 2009; doi: 10.4049/jimmunol.0900921 http://www.jimmunol.org/content/183/2/945 Downloaded from References This article cites 47 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/183/2/945.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 26, 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 © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Cathepsin S Regulates Class II MHC Processing in Human CD4؉ HLA-DR؉ T Cells1 Cristina Maria Costantino,* Hidde L. Ploegh,† and David A. Hafler2* Although it has long been known that human CD4؉ T cells can express functional class II MHC molecules, the role of lysosomal proteases in the T cell class II MHC processing and presentation pathway is unknown. -
Deficiency for the Cysteine Protease Cathepsin L Promotes Tumor
Oncogene (2010) 29, 1611–1621 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 $32.00 www.nature.com/onc ORIGINAL ARTICLE Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermis J Dennema¨rker1,6, T Lohmu¨ller1,6, J Mayerle2, M Tacke1, MM Lerch2, LM Coussens3,4, C Peters1,5 and T Reinheckel1,5 1Institute for Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Freiburg, Germany; 2Department of Gastroenterology, Endocrinology and Nutrition, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany; 3Department of Pathology, University of California, San Francisco, CA, USA; 4Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA and 5Ludwig Heilmeyer Comprehensive Cancer Center and Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany To define a functional role for the endosomal/lysosomal Introduction cysteine protease cathepsin L (Ctsl) during squamous carcinogenesis, we generated mice harboring a constitutive Proteases have traditionally been thought to promote Ctsl deficiency in addition to epithelial expression of the invasive growth of carcinomas, contributing to the the human papillomavirus type 16 oncogenes (human spread and homing of metastasizing cancer cells (Dano cytokeratin 14 (K14)–HPV16). We found enhanced tumor et al., 1999). Proteases that function outside tumor cells progression and metastasis in the absence of Ctsl. As have been implicated in these processes because of their tumor progression in K14–HPV16 mice is dependent well-established release from tumors, causing the break- on inflammation and angiogenesis, we examined immune down of basement membranes and extracellular matrix. cell infiltration and vascularization without finding any Thus, extracellular proteases may in part facilitate effect of the Ctsl genotype. -
Peptidoglycan Crosslinking Relaxation Plays An
Peptidoglycan Crosslinking Relaxation Plays an Important Role in Staphylococcus aureus WalKR-Dependent Cell Viability Aurelia Delauné, Olivier Poupel, Adeline Mallet, Yves-Marie Coïc, Tarek Msadek, Sarah Dubrac To cite this version: Aurelia Delauné, Olivier Poupel, Adeline Mallet, Yves-Marie Coïc, Tarek Msadek, et al.. Peptidoglycan Crosslinking Relaxation Plays an Important Role in Staphylococcus aureus WalKR-Dependent Cell Vi- ability. PLoS ONE, Public Library of Science, 2011, 6 (2), pp.e17054. 10.1371/journal.pone.0017054. pasteur-02870016 HAL Id: pasteur-02870016 https://hal-pasteur.archives-ouvertes.fr/pasteur-02870016 Submitted on 16 Jun 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Peptidoglycan Crosslinking Relaxation Plays an Important Role in Staphylococcus aureus WalKR- Dependent Cell Viability Aurelia Delaune1,2, Olivier Poupel1,2, Adeline Mallet3, Yves-Marie Coic4,5, Tarek Msadek1,2*, Sarah Dubrac1,2 1 Institut Pasteur, Biology of Gram-Positive Pathogens, Department of Microbiology, Paris, France, 2 CNRS, URA 2172, Paris, France, 3 Institut Pasteur, Ultrastructural Microscopy Platform, Imagopole, Paris, France, 4 Institut Pasteur, Chemistry of Biomolecules, Department of Structural Biology and Chemistry, Paris, France, 5 CNRS, URA 2128, Paris, France Abstract The WalKR two-component system is essential for viability of Staphylococcus aureus, a major pathogen. -
A Cysteine Protease Inhibitor Blocks SARS-Cov-2 Infection of Human and Monkey Cells
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.23.347534; this version posted October 30, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. A cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells Drake M. Mellott,1 Chien-Te Tseng,3 Aleksandra Drelich,3 Pavla Fajtová,4,5 Bala C. Chenna,1 Demetrios H. Kostomiris1, Jason Hsu,3 Jiyun Zhu,1 Zane W. Taylor,2,9 Vivian Tat,3 Ardala Katzfuss,1 Linfeng Li,1 Miriam A. Giardini,4 Danielle Skinner,4 Ken Hirata,4 Sungjun Beck4, Aaron F. Carlin,8 Alex E. Clark4, Laura Beretta4, Daniel Maneval6, Felix Frueh,6 Brett L. Hurst,7 Hong Wang,7 Klaudia I. Kocurek,2 Frank M. Raushel,2 Anthony J. O’Donoghue,4 Jair Lage de Siqueira-Neto,4 Thomas D. Meek1.*, and James H. McKerrow#4,* Departments of Biochemistry and Biophysics1 and Chemistry,2 Texas A&M University, 301 Old Main Drive, College Station, Texas 77843, 3Department of Microbiology and Immunology, University of Texas, Medical Branch, 3000 University Boulevard, Galveston, Texas, 77755-1001, 4Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 5Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 16610 Prague, Czech Republic, 6Selva Therapeutics, and 7Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, Utah, 84322, 8Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.9Current address: Biological Sciences Division, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99353.