Studies of Structure and Function of Tripeptidyl-Peptidase II
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The Global Architecture Shaping the Heterogeneity and Tissue-Dependency of the MHC Class I Immunopeptidome Is Evolutionarily Conserved
bioRxiv preprint doi: https://doi.org/10.1101/2020.09.28.317750; this version posted September 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The Global Architecture Shaping the Heterogeneity and Tissue-Dependency of the MHC Class I Immunopeptidome is Evolutionarily Conserved Authors Peter Kubiniok†1, Ana Marcu†2,3, Leon Bichmann†2,4, Leon Kuchenbecker4, Heiko Schuster1,5, David Hamelin1, Jérome Despault1, Kevin Kovalchik1, Laura Wessling1, Oliver Kohlbacher4,7,8,9,10 Stefan Stevanovic2,3,6, Hans-Georg Rammensee2,3,6, Marian C. Neidert11, Isabelle Sirois1, Etienne Caron1,12* Affiliations *Corresponding and Leading author: Etienne Caron ([email protected]) †Equal contribution to this work 1CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada 2Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Baden-Württemberg, 72076, Germany. 3Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Baden-Württemberg, 72076, Germany. 4Applied Bioinformatics, Dept. of Computer Science, University of Tübingen, Tübingen, Baden- Württemberg, 72074, Germany. 5Immatics Biotechnologies GmbH, Tübingen, 72076, Baden-Württemberg, Germany. 6DKFZ Partner Site Tübingen, German Cancer Consortium (DKTK), Tübingen, Baden- Württemberg, 72076, Germany. 7Institute for Bioinformatics and Medical Informatics, -
Enzymatic Encoding Methods for Efficient Synthesis Of
(19) TZZ__T (11) EP 1 957 644 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C12N 15/10 (2006.01) C12Q 1/68 (2006.01) 01.12.2010 Bulletin 2010/48 C40B 40/06 (2006.01) C40B 50/06 (2006.01) (21) Application number: 06818144.5 (86) International application number: PCT/DK2006/000685 (22) Date of filing: 01.12.2006 (87) International publication number: WO 2007/062664 (07.06.2007 Gazette 2007/23) (54) ENZYMATIC ENCODING METHODS FOR EFFICIENT SYNTHESIS OF LARGE LIBRARIES ENZYMVERMITTELNDE KODIERUNGSMETHODEN FÜR EINE EFFIZIENTE SYNTHESE VON GROSSEN BIBLIOTHEKEN PROCEDES DE CODAGE ENZYMATIQUE DESTINES A LA SYNTHESE EFFICACE DE BIBLIOTHEQUES IMPORTANTES (84) Designated Contracting States: • GOLDBECH, Anne AT BE BG CH CY CZ DE DK EE ES FI FR GB GR DK-2200 Copenhagen N (DK) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • DE LEON, Daen SK TR DK-2300 Copenhagen S (DK) Designated Extension States: • KALDOR, Ditte Kievsmose AL BA HR MK RS DK-2880 Bagsvaerd (DK) • SLØK, Frank Abilgaard (30) Priority: 01.12.2005 DK 200501704 DK-3450 Allerød (DK) 02.12.2005 US 741490 P • HUSEMOEN, Birgitte Nystrup DK-2500 Valby (DK) (43) Date of publication of application: • DOLBERG, Johannes 20.08.2008 Bulletin 2008/34 DK-1674 Copenhagen V (DK) • JENSEN, Kim Birkebæk (73) Proprietor: Nuevolution A/S DK-2610 Rødovre (DK) 2100 Copenhagen 0 (DK) • PETERSEN, Lene DK-2100 Copenhagen Ø (DK) (72) Inventors: • NØRREGAARD-MADSEN, Mads • FRANCH, Thomas DK-3460 Birkerød (DK) DK-3070 Snekkersten (DK) • GODSKESEN, -
Molecular Markers of Serine Protease Evolution
The EMBO Journal Vol. 20 No. 12 pp. 3036±3045, 2001 Molecular markers of serine protease evolution Maxwell M.Krem and Enrico Di Cera1 ment and specialization of the catalytic architecture should correspond to signi®cant evolutionary transitions in the Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, history of protease clans. Evolutionary markers encoun- MO 63110-1093, USA tered in the sequences contributing to the catalytic apparatus would thus give an account of the history of 1Corresponding author e-mail: [email protected] an enzyme family or clan and provide for comparative analysis with other families and clans. Therefore, the use The evolutionary history of serine proteases can be of sequence markers associated with active site structure accounted for by highly conserved amino acids that generates a model for protease evolution with broad form crucial structural and chemical elements of applicability and potential for extension to other classes of the catalytic apparatus. These residues display non- enzymes. random dichotomies in either amino acid choice or The ®rst report of a sequence marker associated with serine codon usage and serve as discrete markers for active site chemistry was the observation that both AGY tracking changes in the active site environment and and TCN codons were used to encode active site serines in supporting structures. These markers categorize a variety of enzyme families (Brenner, 1988). Since serine proteases of the chymotrypsin-like, subtilisin- AGY®TCN interconversion is an uncommon event, it like and a/b-hydrolase fold clans according to phylo- was reasoned that enzymes within the same family genetic lineages, and indicate the relative ages and utilizing different active site codons belonged to different order of appearance of those lineages. -
Processing of Antigenic Peptides by Aminopeptidases
June 2004 Biol. Pharm. Bull. 27(6) 777—780 (2004) 777 Current Topics Aminopeptidases in Health and Disease Processing of Antigenic Peptides by Aminopeptidases Akira HATTORI* and Masafumi TSUJIMOTO Laboratory of Cellular Biochemistry, RIKEN; 2–1 Hirosawa, Wako, Saitama 351–0198, Japan. Received January 7, 2004 Antigenic peptides presented to major histocompatibility complex (MHC) class I molecules are generated in the cytosol during degradation of cellular proteins by the ubiquitin-proteasome proteolytic pathway. Proteasome can generate N-extended precursors as well as final epitopes, and then the precursors are processed to mature epitopes by aminopeptidases. Both cytosolic peptidases (i.e. puromycin-sensitive aminopeptidase, bleomycin hy- drolase and interferon-g-inducible leucine aminopeptidase) and recently identified metallo-aminopeptidase lo- cated in the endoplasmic reticulum (i.e. adipocyte-derived leucine aminopeptidase/endoplasmic reticulum aminopeptidase 1 and leukocyte-derived arginine aminopeptidase) can generate final epitopes from precursor peptides. Some of these aminopeptidases are also considered to destroy certain antigenic peptides to limit the antigen presentation. Taken together, it is getting evident that aminopeptidases located in the cytosol and the lumen of endoplasmic reticulum play important roles in the generation of antigenic peptides presented to MHC class I molecules. Key words aminopeptidase; antigen processing; major histocompatibility complex (MHC) class I; antigen presentation; protea- some; protein degradation -
Effects of Glycosylation on the Enzymatic Activity and Mechanisms of Proteases
International Journal of Molecular Sciences Review Effects of Glycosylation on the Enzymatic Activity and Mechanisms of Proteases Peter Goettig Structural Biology Group, Faculty of Molecular Biology, University of Salzburg, Billrothstrasse 11, 5020 Salzburg, Austria; [email protected]; Tel.: +43-662-8044-7283; Fax: +43-662-8044-7209 Academic Editor: Cheorl-Ho Kim Received: 30 July 2016; Accepted: 10 November 2016; Published: 25 November 2016 Abstract: Posttranslational modifications are an important feature of most proteases in higher organisms, such as the conversion of inactive zymogens into active proteases. To date, little information is available on the role of glycosylation and functional implications for secreted proteases. Besides a stabilizing effect and protection against proteolysis, several proteases show a significant influence of glycosylation on the catalytic activity. Glycans can alter the substrate recognition, the specificity and binding affinity, as well as the turnover rates. However, there is currently no known general pattern, since glycosylation can have both stimulating and inhibiting effects on activity. Thus, a comparative analysis of individual cases with sufficient enzyme kinetic and structural data is a first approach to describe mechanistic principles that govern the effects of glycosylation on the function of proteases. The understanding of glycan functions becomes highly significant in proteomic and glycomic studies, which demonstrated that cancer-associated proteases, such as kallikrein-related peptidase 3, exhibit strongly altered glycosylation patterns in pathological cases. Such findings can contribute to a variety of future biomedical applications. Keywords: secreted protease; sequon; N-glycosylation; O-glycosylation; core glycan; enzyme kinetics; substrate recognition; flexible loops; Michaelis constant; turnover number 1. -
Towards Therapy for Batten Disease
Towards therapy for Batten disease Mariana Catanho da Silva Vieira MRC Laboratory for Molecular Cell Biology University College London PhD Supervisor: Dr Sara E Mole A thesis submitted for the degree of Doctor of Philosophy University College London September 2014 Declaration I, Mariana Catanho da Silva Vieira, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Abstract The gene underlying the classic neurodegenerative lysosomal storage disorder (LSD) juvenile neuronal ceroid lipofuscinosis (JNCL) in humans, CLN3, encodes a polytopic membrane spanning protein of unknown function. Several studies using simpler models have been performed in order to further understand this protein and its pathological mechanism. Schizosaccharomyces pombe provides an ideal model organism for the study of CLN3 function, due to its simplicity, genetic tractability and the presence of a single orthologue of CLN3 (Btn1p), which exhibits a functional profile comparable to its human counterpart. In this study, this model was used to explore the effect of different mutations in btn1 as well as phenotypes arising from complete deletion of the gene. Different btn1 mutations have different effects on the protein function, underlining different phenotypes and affecting the levels of expression of Btn1p. So far, there is no cure for JNCL and therefore it is of great importance to identify novel lead compounds that can be developed for disease therapy. To identify these compounds, a drug screen with btn1Δ cells based on their sensitivity to cyclosporine A, was developed. Positive hits from the screen were validated and tested for their ability to rescue other specific phenotypes also associated with the loss of btn1. -
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. -
Enzymatic Hydrolysis and Peptide Mapping of Potato Pulp Protein
Enzymatic Hydrolysis and Peptide Mapping of Potato Pulp Protein Von der Naturwissenschaftlichen Fakultät der Universität Hannover zur Erlangung des Grades Doktorin der Naturwissenschaften Dr. rer. nat. genehmigte Dissertation von Chulaporn Kamnerdpetch, M.Sc. geboren in Bangkok, Thailand Hannover 2006 Hauptreferent Prof. Dr. Thomas Scheper Institut für Technische Chemie Universität Hannover Koreferent Prof. Dr. Bernd Hitzmann Institut für Technische Chemie Universität Hannover Tag der Promotion 29. Mai 2006 Erklärung Ich versichere, dass ich diese Dissertation selbstständig und nur unter Verwendung der angegebenen Hilfsmittel und Quellen durchgeführt habe. Diese Arbeit wurde nicht als Diplomarbeit oder ähnliche Prüfungsarbeit verwendet. Chulaporn Kamnerdpetch Hannover, den 29. Mai 2006 ACKNOWLEDGEMENTS This thesis is the result of my four years research work whereby I have been accompanied and supported by many people. It is a pleasant aspect that I have now the opportunity to express my sincere gratitude for all of them who made this thesis possible. The first person I would like to thank is my supervisor Prof. Dr. Thomas Scheper for giving me the opportunity to take part on the doctoral program at the Institut für Technische Chemie der Universität Hannover. I appreciate very much for his enthusiastic and enthusing support. He gave me an encourage independent thinking and the freedom to try out my ways. I would like to thank to Prof. Dr. Bernd Hitzmann for his kindness acceptance as my co-referee. I wish to express my thank to Dr. Cornelia Kasper for preparing my publication and proof reading. It is a great pleasure for me to thank Dr. Pichai Namparkai for proof reading as well. -
Supplemental Materials Supplemental Table 1
Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2016 Supplemental Materials Supplemental Table 1. The differentially expressed proteins from rat pancreas identified by proteomics (SAP vs. SO) No. Protein name Gene name ratio P value 1 Metallothionein Mt1m 3.35 6.34E-07 2 Neutrophil antibiotic peptide NP-2 Defa 3.3 8.39E-07 3 Ilf2 protein Ilf2 3.18 1.75E-06 4 Numb isoform o/o rCG 3.12 2.73E-06 5 Lysozyme Lyz2 3.01 5.63E-06 6 Glucagon Gcg 2.89 1.17E-05 7 Serine protease HTRA1 Htra1 2.75 2.97E-05 8 Alpha 2 macroglobulin cardiac isoform (Fragment) 2.75 2.97E-05 9 Myosin IF (Predicted) Myo1f 2.65 5.53E-05 10 Neuroendocrine secretory protein 55 Gnas 2.61 7.60E-05 11 Matrix metallopeptidase 8 Mmp8 2.57 9.47E-05 12 Protein Tnks1bp1 Tnks1bp1 2.53 1.22E-04 13 Alpha-parvin Parva 2.47 1.78E-04 14 C4b-binding protein alpha chain C4bpa 2.42 2.53E-04 15 Protein KTI12 homolog Kti12 2.41 2.74E-04 16 Protein Rab11fip5 Rab11fip5 2.41 2.84E-04 17 Protein Mcpt1l3 Mcpt1l3 2.33 4.43E-04 18 Phospholipase B-like 1 Plbd1 2.33 4.76E-04 Aldehyde dehydrogenase (NAD), cytosolic 19 2.32 4.93E-04 (Fragments) 20 Protein Dpy19l2 Dpy19l2 2.3 5.68E-04 21 Regenerating islet-derived 3 alpha, isoform CRA_a Reg3a 2.27 6.74E-04 22 60S acidic ribosomal protein P1 Rplp1 2.26 7.22E-04 23 Serum albumin Alb 2.25 7.98E-04 24 Ribonuclease 4 Rnase4 2.24 8.25E-04 25 Cct-5 protein (Fragment) Cct5 2.24 8.52E-04 26 Protein S100-A9 S100a9 2.22 9.71E-04 27 Creatine kinase M-type Ckm 2.21 1.00E-03 28 Protein Larp4b Larp4b 2.18 1.25E-03 -
Proquest Dissertations
urn u Ottawa L'Universitd canadienne Canada's university FACULTE DES ETUDES SUPERIEURES l^^l FACULTY OF GRADUATE AND ET POSTDOCTORALES u Ottawa POSTDOCTORAL STUDIES I.'University emiadienne Canada's university Charles Gyamera-Acheampong AUTEUR DE LA THESE / AUTHOR OF THESIS Ph.D. (Biochemistry) GRADE/DEGREE Biochemistry, Microbiology and Immunology FACULTE, ECOLE, DEPARTEMENT / FACULTY, SCHOOL, DEPARTMENT The Physiology and Biochemistry of the Fertility Enzyme Proprotein Convertase Subtilisin/Kexin Type 4 TITRE DE LA THESE / TITLE OF THESIS M. Mbikay TIRECTWRTDIRICTR^ CO-DIRECTEUR (CO-DIRECTRICE) DE LA THESE / THESIS CO-SUPERVISOR EXAMINATEURS (EXAMINATRICES) DE LA THESE/THESIS EXAMINERS A. Basak G. Cooke F .Kan V. Mezl Gary W. Slater Le Doyen de la Faculte des etudes superieures et postdoctorales / Dean of the Faculty of Graduate and Postdoctoral Studies Library and Archives Bibliotheque et 1*1 Canada Archives Canada Published Heritage Direction du Branch Patrimoine de I'edition 395 Wellington Street 395, rue Wellington OttawaONK1A0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre reference ISBN: 978-0-494-59504-6 Our file Notre reference ISBN: 978-0-494-59504-6 NOTICE: AVIS: The author has granted a non L'auteur a accorde une licence non exclusive exclusive license allowing Library and permettant a la Bibliotheque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par telecommunication ou par I'lnternet, prefer, telecommunication or on the Internet, distribuer et vendre des theses partout dans le loan, distribute and sell theses monde, a des fins commerciales ou autres, sur worldwide, for commercial or non support microforme, papier, electronique et/ou commercial purposes, in microform, autres formats. -
Leishmania (L.) Amazonensis Peptidase Activities Inside the Living Cells and in Their Lysates
Molecular & Biochemical Parasitology 184 (2012) 82–89 Contents lists available at SciVerse ScienceDirect Molecular & Biochemical Parasitology Leishmania (L.) amazonensis peptidase activities inside the living cells and in their lysates a a b c a Elide E. Caroselli , Diego M. Assis , Clara L. Barbiéri , Wagner A.S. Júdice , Maria A. Juliano , d a,∗ Marcos L. Gazarini , Luiz Juliano a Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, Brazil b Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, Brazil c Centro Interdisciplinar de Investigac¸ ão Bioquímica, Universidade de Mogi das Cruzes, Av. Dr. Cândido Xavier de Almeida Souza 200, 08780-911 Mogi das Cruzes, Brazil d Department of Biosciences, Universidade Federal de São Paulo, Santos, Brazil a r t i c l e i n f o a b s t r a c t Article history: In this study we investigated the peptidase activity in Leishmania (L.) amazonensis live amastigote by con- Received 24 November 2011 focal microscopy using peptidyl-MCA as substrates, the hydrolysis of which releases the MCA fluorophore Received in revised form 13 March 2012 inside the cells. Cell pre-treatment with peptidase inhibitors indicated the presence of cysteine and ser- Accepted 27 April 2012 ine peptidases. It was noteworthy that Leishmania amastigotes incorporate only substrates (Z-FR-MCA, Available online 6 May 2012 Z-RR-MCA) or inhibitors (E64, TLCK) containing positively charged groups. The peptidase activities in the supernatants of amastigotes and promastigotes lysates were also evaluated with the same peptidyl-MCA Keywords: substrates and inhibitors in the pH range 4.5–9.0. -
Marine Organisms: a Source of Biomedically Relevant Metallo M1
Marine organisms : a source of biomedically relevant metallo M1, M2 and M17 exopeptidase inhibitors Isel Pascual Alonso, Laura Rivera Méndez, Fabiola Almeida, Mario Ernesto Valdés Tresano, Yarini Arrebola Sánchez, Aida Hernández-Zanuy, Luis Álvarez-Lajonchere, Dagmara Díaz, Belinda Sánchez, Isabelle Florent, et al. To cite this version: Isel Pascual Alonso, Laura Rivera Méndez, Fabiola Almeida, Mario Ernesto Valdés Tresano, Yarini Arrebola Sánchez, et al.. Marine organisms : a source of biomedically relevant metallo M1, M2 and M17 exopeptidase inhibitors. REVISTA CUBANA DE CIENCIAS BIOLÓGICAS, 2020, 8 (2), pp.1- 36. hal-02944434 HAL Id: hal-02944434 https://hal.archives-ouvertes.fr/hal-02944434 Submitted on 21 Sep 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. REVISTA CUBANA DE CIENCIAS BIOLÓGICAS http://www.rccb.uh.cu ARTÍCULO DE REVISIÓN Marine organisms: a source of biomedically relevant metallo M1, M2 and M17 exopeptidase inhibitors Los organismos marinos: Fuente de inhibidores de exopeptidasas de tipo metalo M1, M2 y M17 de relevancia biomédica Isel Pascual Alonso1 , Laura Rivera Méndez1 , Fabiola Almeida1 , Mario Ernesto Valdés Tresanco1,2 , Yarini Arrebola Sánchez1 , Aida Hernández-Zanuy3 , Luis Álvarez-Lajonchere4 , Dagmara Díaz1 , Belinda Sánchez5 , Isabelle Florent6 , Marjorie Schmitt7 , Miguel Cisneros8 , Jean Louis Charli8 1 Center for Protein Studies, Faculty of ABSTRACT Biology, University of Havana, Cuba.