Refine
Year of publication
Document Type
- Doctoral Thesis (137)
- Article (48)
Has Fulltext
- yes (185)
Is part of the Bibliography
- no (185)
Keywords
- - (47)
- Biokatalyse (23)
- Proteindesign (15)
- Enzym (13)
- biocatalysis (10)
- Biotechnologie (8)
- Biochemie (7)
- RNA (7)
- Ribozym (7)
- Biocatalysis (6)
- Protein-Engineering (6)
- Enzyme (5)
- Hydrolasen (5)
- Struktur (5)
- protein engineering (5)
- Elektrochemie (4)
- Gerichtete Evolution (4)
- Molybdopterin (4)
- Protein Engineering (4)
- RNS (4)
- Thermodynamik (4)
- Baeyer-Villiger monooxygenase (3)
- Baeyer-Villiger-Oxidation (3)
- Biokonversion (3)
- DNA-Wirkstoff-Interaktion (3)
- DNA-drug interaction (3)
- DNS (3)
- Diabetes mellitus (3)
- Enzymkatalyse (3)
- Esterasen (3)
- Gold (3)
- Indolochinolin (3)
- Magnetische Kernresonanz (3)
- Massenspektrometrie (3)
- Metabolomics (3)
- Monooxygenasen (3)
- Nucleinsäuren (3)
- Oxidativer Stress (3)
- Oxidoreduktase (3)
- Promiskuität (3)
- Protein engineering (3)
- RNS-Reparatur (3)
- RNS-Synthese (3)
- Rasterkraftmikroskopie (3)
- Reaktionsmechanismus (3)
- SELEX (3)
- Substratspezifität (3)
- Titandioxid (3)
- Transaminasen (3)
- Transaminases (3)
- asymmetric synthesis (3)
- catalytic promiscuity (3)
- electrochemistry (3)
- regioselectivity (3)
- transesterification (3)
- Acyltransferase (2)
- Amine (2)
- Arylesterase (2)
- Asymmetric synthesis (2)
- Baeyer-Villiger Monooxygenase (2)
- Benzazaphosphole (2)
- Biosensor (2)
- Chemie (2)
- Chiral amines (2)
- Chirale Amine (2)
- Cyclovoltammetrie (2)
- Cytidindesaminierung (2)
- DNA Triplex (2)
- DNA triplex (2)
- Enantioselektivität (2)
- Enoatreduktase (2)
- Flavonoide (2)
- Fluoreszenzmarkierung (2)
- G-quadruplexes (2)
- Haloalkan Dehalogenase (2)
- Heterologe Genexpression (2)
- Hydrolases (2)
- Hydroxyl (2)
- Immobilisierung (2)
- Ketoreductase (2)
- Kristallographie (2)
- Kristallstruktur (2)
- Lipase (2)
- Metabolismus (2)
- Molekulardesign (2)
- Molekulardynamik (2)
- Molybdenum (2)
- NMR spectroscopy (2)
- Pankreatitis (2)
- Phosphine (2)
- Proteine (2)
- Pterin (2)
- Schweineleberesterase (2)
- Selektionsassay (2)
- Simulation (2)
- Spektroskopie (2)
- Staphylococcus aureus (2)
- Strukturbiologie (2)
- Tetracyclinrepressor (2)
- Transaminase (2)
- Transkriptionspriming (2)
- Twinribozym (2)
- Wasserstoffperoxid (2)
- acyl transfer (2)
- acyltransferase (2)
- antibacterial activity (2)
- atomic force microscopy (2)
- biosensor (2)
- directed evolution (2)
- enzyme cascade (2)
- enzyme catalysis (2)
- high-throughput screening (2)
- hydrolases (2)
- indoloquinoline (2)
- katalytische Promiskuität (2)
- metabolomics (2)
- natural products (2)
- plastic degradation (2)
- quadruplex (2)
- rational protein design (2)
- rationales Proteindesign (2)
- redox chemistry (2)
- ribozyme (2)
- structure-activity (2)
- synthesis (2)
- thermodynamics (2)
- transaminases (2)
- transcription priming (2)
- twin ribozyme (2)
- -Enzym (1)
- 1,4-naphthoquinones (1)
- 1-deoxy sphingolipids (1)
- 3-Bis(Silyl Enol Ethers) (1)
- 31P-NMR (1)
- 3DM (1)
- 4070512-2 (1)
- 4165547-3 (1)
- 4193016-2 (1)
- 4248339-6 (1)
- 4323543-8 (1)
- 4441960-0 (1)
- 4796824-2 (1)
- 7 beta Hydroxylierung (1)
- 7β-Hydroxylierung (1)
- <i>Bacillus subtilis</i> (1)
- <i>S. aureus</i> (1)
- <i>S. pneumoniae</i> (1)
- <i>Staphylococcus aureus</i> (1)
- API Drug synthesis (1)
- Acyltransfer (1)
- Acyltransferasen (1)
- Adenosindesaminierung (1)
- Adhesion (1)
- Adsorption (1)
- Aktive Zentren (1)
- Akute Bauchspeicheldrüsenentzündung (1)
- Akute Pankreatitis (1)
- Alcohol dehydrogenase (1)
- Alkanolamine (1)
- Alkohol (1)
- Alkohole (1)
- Alphaherpesviren (1)
- Alphaherpesvirus (1)
- Amin-Transaminasen (1)
- Amine transaminase, ketoreductase (1)
- Amino Alcohol (1)
- Aminoacylierung (1)
- Aminoalkohol (1)
- Aminosäuren (1)
- Amperometric detection; EstraMonitor (1)
- Amperometrische Detektion; EstraMonitor (1)
- Analytische Chemie (1)
- Annotation (1)
- Anti-cancer and anti-microbials (1)
- Antibiotikum (1)
- Antioxidans (1)
- Antiphospholipidsyndrom (1)
- Antiterminator-Proteine (1)
- Aptamer (1)
- Aptamers (1)
- Aptazym (1)
- Aquaporins (1)
- Aquatic Interfaces (1)
- Aryl fluorides (1)
- Arzneimitteldesign (1)
- Aspzinkin (1)
- Assemblin (1)
- Atmosphärendruckplasma (1)
- Autoantikörper (1)
- Azaphospholderivat (1)
- BVMO (1)
- Bacillus subtilis (1)
- Baclofen (1)
- Baeyer-Villiger monooxygenases (1)
- Bauchspeicheldrüsenentzündung (1)
- Benzazaphospholes (1)
- Biaryle (1)
- Biocatalytic alkylation (1)
- Biogeochemie (1)
- Biokatalyse , Enzym , Alkohol , Amine , Enzymkatalyse , Asymmetrische Katalyse (1)
- Biokatalyse , Organische Synthese , Enzym , Prozessoptimierung (1)
- Biokompatibilität (1)
- Biomimetic membrane; cold physical plasma;membrane oxidation; lipid bilayer; electrochemistry; mass spectrometry; atomic force microscopy (1)
- Biophysikalische Chemie (1)
- Bioreaktor (1)
- Biosynthesis of bile acids (1)
- Biotechnologie; Biokatalyse; Metagenom; Enzym (1)
- Butyrolactonderivate (1)
- C-F activation (1)
- CAL-A (1)
- CANDLE/PRAAS (1)
- CAZymes (1)
- CODEHOP (1)
- Calcium (1)
- Campher (1)
- Caprolacton <epsilon-> (1)
- Carbamoylase (1)
- Carboxylester-Hydrolasen (1)
- Carboxylesterase (1)
- Cathepsin B (1)
- Cathepsine (1)
- Ceramide (1)
- Chalconisomerase (1)
- Chemical Stability (1)
- Chemische Stabilität (1)
- Chemische Synthese (1)
- Chemo-enzymatic synthesis (1)
- Chinhydron (1)
- Chiral amine (1)
- Chondroitinsulfate (1)
- Chronische Bauchspeicheldrüsenentzündung (1)
- Chronische Pankreatitis (1)
- Cofaktor (1)
- Collagen (1)
- Corrosion-electrochemical behaviour (1)
- Cross-coupling (1)
- Cyanoethyl (1)
- Cyclisation (1)
- Cycloalkanonmonooxygenase (1)
- Cyclohexanon-Monooxygenase (1)
- Cyclohexanone monooxygenase (1)
- Cylindrocarpon radicicola (1)
- Cystatin C (1)
- Cytochrom P450 Monooxygenase (1)
- Cytochrome P-450 (1)
- Cytotoxizität (1)
- C–C bond cleavage (1)
- DNA (1)
- DNA-Wirkstoff-Struktur (1)
- DNA-drug structure (1)
- DNA-microarray (1)
- DNAzym (1)
- DNAzyme (1)
- Darm (1)
- Dehydrocyclisation (1)
- Desorption (1)
- Diastereomere (1)
- Dihydropyrimidinase (1)
- Directed evolution (1)
- Dithiol (1)
- Dithiolene (1)
- Durchflusscytometrie (1)
- Eicosanoide (1)
- Eintopfreaktion (1)
- Electrochemical Stability (1)
- Electrochemie (1)
- Elektrochemische Stabilität (1)
- Elektrochemischer Sensor (1)
- Elektrokatalyse (1)
- Enantiopreference (1)
- Enzyme Discovery (1)
- Enzyme identification (1)
- Enzymidentifizierung (1)
- Enzymkaskade (1)
- Enzymkinetik (1)
- Epoxid-Hydrolase (1)
- Epoxidhydrolase (1)
- Error-prone PCR (1)
- Erucic acid (1)
- Ethylen Oligomerisation (1)
- Ethylene oligomerisation (1)
- Ethylene oligomerization (1)
- Ethylenoligomerisation (1)
- Eubacterium ramulus (1)
- Familie-VIII-Carboxylesterase (1)
- Fatty acid enrichment (1)
- Fermentation (1)
- Festphase (1)
- Festphasensynthese (1)
- Fibronectin (1)
- Fibrose (1)
- Flavine (1)
- Flavinemononucleotide (1)
- Flavinmononukleotid (1)
- Flavivirus (1)
- Fließinjektionsanalyse (1)
- Funktionalisierung <Chemie> (1)
- Fusionsprotein (1)
- G-Quadruplex (1)
- GC-MS (1)
- Genbibliothek (1)
- Gendrift (1)
- Genregulation (1)
- Gentherapie (1)
- Gerüstprotein (1)
- Gleichgewicht (1)
- Glycolysis (1)
- Glykosaminoglykane (1)
- Gold-Nanopartikel (1)
- Gondoic acid (1)
- Graphische Darstellung (1)
- HEV (1)
- Hairpin-Ribozym (1)
- Hairpinribozym (1)
- Haloalkan-Dehalogenase (1)
- Hefeartige Pilze (1)
- Hepatitis-E-Virus , Polymerase-Kettenreaktion , Microarray , West-Nil-Virus , Flaviviren , RNS-Viren , Genotypisierung (1)
- Herpesviren (1)
- Herpesviridae (1)
- Heterocycle synthesis (1)
- Heterocyclische Verbindungen (1)
- High throughput screening (1)
- Hirudin (1)
- Hirudin‐like factors (1)
- Histidin (1)
- Histidinphosphorylierung (1)
- Hyaluronsäure (1)
- Hybrid Liganden (1)
- Hybrid ligand (1)
- Hydantoinase-Prozess (1)
- Hydrogenphosphate (1)
- Identifikation (1)
- Imin-Reduktase (1)
- Imine (1)
- Iminreduktase (1)
- Immobilization (1)
- Immunantwort (1)
- Immunsystem (1)
- Impedance Spectroscopy (1)
- Impedanzspektroskopie (1)
- Implant (1)
- Implantat (1)
- In situ product recovery (1)
- Industrie (1)
- Infektionen (1)
- Integrin (1)
- Integrin αIIbβ3 (1)
- Integrin αiibβ3 (1)
- Interleukin 33 (1)
- Isopropylamine (1)
- Isothermale Titrationskalorimetrie (1)
- KHV (1)
- KHVD (1)
- Karzinom (1)
- Kaskade (1)
- Kaskadenreaktion (1)
- Katalyse (1)
- Ketene (1)
- Ketoreduktase (1)
- Kip1 (1)
- Klarzelliges Nierenzellkarzinom (1)
- Klinische Pathologie (1)
- Kohlendioxid (1)
- Komplexe (1)
- Kontinuierliche gerichtete Evolution (1)
- Korrosion (1)
- Korrosionselektrochemische Verhalten (1)
- Kraftfeld-Rechnung (1)
- Kristallfläche (1)
- Künstliche Evolution (1)
- LC-MS (1)
- LCA (1)
- Landsat (1)
- Ligand (1)
- Ligand-DNA-Interaktion (1)
- Ligation (1)
- Limnologie (1)
- Linker (1)
- Lipasen (1)
- Lipases (1)
- Lipid Modification (1)
- Lithocholsäure (1)
- Lysosomen (1)
- Makrophagen (1)
- Meerespilze (1)
- Membrane (1)
- Metabolism (1)
- Metabolom (1)
- Methylation (1)
- Methyltransferase (1)
- MoCo (1)
- Modelle des Molybdän-Cofaktors (1)
- Modellverbindungen (1)
- Molecular Modeling (1)
- Molecular Modelling (1)
- Molecular modeling (1)
- Molecular modelling (1)
- Molybdenum Cofactor (1)
- Molybdenum cofactor (moco) (1)
- Molybdenum cofactor (moco) models (1)
- Molybdenum mediated pentathiepin synthesis (1)
- Molybdän-Cofaktor (1)
- Molybdän-Cofaktor-Defizienz (1)
- Monooxygenase (1)
- Mutagenese (1)
- N-Acyl-L-Homoserinlakton (1)
- N-Aryl Phosphinoglycines (1)
- N-heterocyclic olefins (1)
- N-substituierter Phosphanylglycine (1)
- NNMT (1)
- Naringenin (1)
- Naturstoff (1)
- Nickel (1)
- Nickel catalysts (1)
- Nickelkatalysator (1)
- Niere (1)
- Nitric oxide (1)
- Nnucleophilic substitution (1)
- Nucleoside modification and labeling (1)
- Nukleinsäuren (1)
- Nukleosidanaloga (1)
- Nukleoside (1)
- OAT Reaction (1)
- ONX-0914 (1)
- Oberflächenbehandlung (1)
- Oberflächenmodifizierung (1)
- Oberflächenveränderung (1)
- OleP (1)
- Oligomerisation (1)
- Oligonukleotid Konjugate (1)
- One‐pot reaction (1)
- Optisch active Dithiolene (1)
- Organic Matter (1)
- Organischer Stoff (1)
- Organschaden (1)
- Oxidoreductase (1)
- Oxidoreductasen (1)
- Oxidoreductases (1)
- Oxidoreduktasen (1)
- Oxidschi (1)
- Oxocarbonsäureester (1)
- P-Arylation (1)
- P450 (1)
- P=C Verbindungen (1)
- P=C-N-Heterocyclen (1)
- P=C-N-Heterocycles (1)
- Pancreatitis (1)
- Passivierung (1)
- Pb-UPD (1)
- Pd/PTABS catalyst (1)
- Pentathiepins (1)
- Peptide (1)
- PestE (1)
- Phase Equilibrium (1)
- Phasengleichgewicht (1)
- Phenylalanin-Ammoniumlyase (1)
- Phloretin (1)
- Phosphane (1)
- Phosphanyl- (1)
- Phosphanylaminosäure (1)
- Phosphanylaniline (1)
- Phosphanylglycine (1)
- Phosphaproline (1)
- Phosphaprolines (1)
- Phosphate Substituted Dithiolene (1)
- Phosphino amino acids (1)
- Phosphinoaminosäuren (1)
- Phosphinoaniline (1)
- Phosphinoanilines (1)
- Phosphinoglycines (1)
- Phospholipase A2 (1)
- Phosphonium glycolates (1)
- Phosphoniumglykolate (1)
- Phosphoniumsalze (1)
- Phosphor-31-NMR-Spektroskopie (1)
- Phosphoramidite (1)
- Phosphorylierung (1)
- Phosphotransferasesystem (1)
- Physikalische Chemie (1)
- Plasmachemie (1)
- Platelet Factor 4 (1)
- Platin (1)
- Platinabscheidung auf Gold (1)
- Plesiocystis pacifica (1)
- Plättchenfaktor 4 (1)
- Polycaprolactone (1)
- Polykristall (1)
- Polyphenole (1)
- Potential – pH Diagram (1)
- Potentiometrie (1)
- Potenzial – pH-Diagramm (1)
- Pr (1)
- Process engineering (1)
- Protease (1)
- Proteases (1)
- Proteinfaltung (1)
- Proteingerüst (1)
- Proteinogene Aminosäuren (1)
- Proteinreinigung (1)
- Proteinsequenz (1)
- Protonen-NMR-Spektroskopie (1)
- Prozesstechnik (1)
- Pseudomonas putida (1)
- Pseudorabies-Virus (1)
- Push–pull imines (1)
- Pyruvatdecarboxylase (1)
- QCM (1)
- QM/MM (1)
- Quadruplex (1)
- Quantenchemie (1)
- Quorum quenching (1)
- Quorum sensing (1)
- RIDD (1)
- RNA engineering (1)
- RNA recombination (1)
- RNA repair (1)
- RNA, modifizierte Nukleoside, Chemische Synthese (1)
- RNA-Reparatur (1)
- RNS-Edierung (1)
- RT-qPCR (1)
- Radikalfänger (1)
- Rasterelektronenmikroskop (1)
- Reaktionskaskade (1)
- Reaktive Sauerstoffspezies (1)
- Redox Biogeochemie (1)
- Redox Biogeochemistry (1)
- Reduktive Aminierung (1)
- Regioselektivität (1)
- Regulatorische T-Zelle (1)
- Rekombination (1)
- Renilla Luciferase (1)
- Repressorproteine (1)
- Resistenz (1)
- Rhenium (1)
- Rhodococcus rhodochrous (1)
- Riboswitch (1)
- Ring-opening polymerization (1)
- Ringöffnungspolymerisation (1)
- Röntgenkristallographie (1)
- Röntgenstrukturanalyse (1)
- SAM analogue (1)
- SNPs (1)
- Schweineleber-Esterase (1)
- Schwermetalle (1)
- Scilab (1)
- Screening (1)
- Sekundärstruktur (1)
- Sensor (1)
- Sensoren (1)
- Serinproteasen (1)
- Small RNA (1)
- Sphingolipide (1)
- Spinmarkierung (1)
- Stabilität (1)
- Steroidmonooxygenase (1)
- Stickstoffmonoxid (1)
- Stoffwechsel (1)
- Streptococcus pneumoniae (1)
- Streptomyces (1)
- Strukturanalyse (1)
- Strukturaufklärung (1)
- Strukturverfeinerung (1)
- Substrat <Chemie> (1)
- Suides Herpesvirus (1)
- Sulfoxidation (1)
- Synthese (1)
- Synthetic Biology (1)
- Synthetic design (1)
- Synthetische Biologie (1)
- Targeted Proteomics (1)
- Temperaturbeständigkeit (1)
- Tetracyclin (1)
- Tetracycline (1)
- Thermal Desorption Spectrometry (1)
- Thermische Desorptionsspektroskopie (1)
- Tierphysiologie (1)
- Titan (1)
- Titration (1)
- Transition Metal Complexes (1)
- Transitional metal catalysis (1)
- Trinukleotid (1)
- Tyrosin-Ammonium-Lyase (1)
- UDCA (1)
- UPR (1)
- Umesterung (1)
- Uncoupling (1)
- Ursodeoxycholsäure (1)
- V-loop (1)
- VEEV (1)
- VHL (1)
- Veresterung (1)
- Voltammetrie (1)
- Vorhersage (1)
- WNV (1)
- Warburg effect (1)
- Wasserhärte (1)
- Water-soluble catalysis (1)
- Wein (1)
- Whole-cell enzyme cascade (1)
- Wirtsorganismus (1)
- Wnt signalling (1)
- Wnt-Signalweg (1)
- X-ray structure (1)
- Zellen (1)
- active centers (1)
- acylation (1)
- acyltransferases (1)
- adaptation (1)
- adenosine deamination (1)
- aging (1)
- airway epithelial cells (1)
- alanine scanning (1)
- alcohol dehydrogenase (1)
- alcohol dehydrogenases (1)
- aldehyde production (1)
- aldehydes (1)
- alkenes (1)
- alpha- Phosphino Amino Acids (1)
- alpha-toxin (1)
- alphaherpesvirus (1)
- amination (1)
- amine transaminase (1)
- amino alcohols (1)
- antibiotic resistance (1)
- antimicrobial (1)
- antimicrobial substance (1)
- antiterminator protein (1)
- aptazyme (1)
- aptazymes (1)
- aquaculture (1)
- aquatische Grenzzonen (1)
- assemblin (1)
- assembly protein (1)
- asymmetric catalysis (1)
- atmospheric-pressure plasma jets (1)
- autoligation (1)
- beta-Catenin (1)
- beta-catenin (1)
- bioactive compounds (1)
- biocatalytic cascades (1)
- biochemical-clinical traits (1)
- bioinformatic (1)
- biological membranes (1)
- bioluminescence (1)
- biomarker (1)
- blood coagulation (1)
- bone erosion (1)
- boronic acids (1)
- bortezomib (1)
- bulk chemical production (1)
- capsid assembly (1)
- carbamoylase (1)
- carbocations (1)
- carbon catabolite repression (1)
- carrageenan (1)
- cascade reaction (1)
- castration-resistant prostate cancer (1)
- ccRCC (1)
- cell cycle regulator (1)
- cell proliferation (1)
- cellular sensitivity (1)
- chalcone isomerase (1)
- chemical ecology (1)
- chemical identification (1)
- chemische Identifizierung (1)
- chiral amines (1)
- chondroitin sulfate (1)
- circular (1)
- cloud removal (1)
- co-infection (1)
- cold physical plasma (1)
- cold physical plasmas (1)
- collagen-induced arthritis (1)
- compensatory growth (1)
- cyclin-dependent kinase inhibitor (1)
- cycloalkanone monooxygenase (1)
- cytidine deamination (1)
- degradation (1)
- dehalogenase (1)
- derivatives (1)
- detergents (1)
- dihedral principal component analysis (1)
- dihydrogen phosphate (1)
- diketocamphane monooxygenase (1)
- diseases (1)
- dithiolene ligand (1)
- duale Substraterkennung (1)
- eQTL (1)
- eicosanoids (1)
- enantioselectivity (1)
- endosymbionts (1)
- enzyme (1)
- enzyme evolution (1)
- enzymes (1)
- epoxide hydrolase (1)
- esterase (1)
- esterases (1)
- extracellular matrix (1)
- eye lens cell membrane (1)
- family VIII carboxylesterase (1)
- fish (live) (1)
- flavin reductase (1)
- flavonoid (1)
- fluorescence (1)
- fluorine (1)
- free radicals (1)
- fusion protein (1)
- gamma-Lactamase (1)
- gamma-lactamase (1)
- genetic (1)
- genetic code expansion (1)
- genetically encoded sensors (1)
- genotyping (1)
- gerichtete Evolution (1)
- glycosaminoglycans (1)
- glycosidases (1)
- glycosidic torsion angles (1)
- gold nanoparticles (1)
- group A streptococcus (1)
- guanosine analogs (1)
- hairpin-ribozyme (1)
- halides (1)
- haloalkane (1)
- haloalkane dehalogenases (1)
- haloperoxidase (1)
- heavy metal (1)
- heterologous gene expression (1)
- histidine (1)
- host pathogen interactions (1)
- hyaluronic acid (1)
- hydantoinase (1)
- hydantoinase-process (1)
- hydrogen bond (1)
- hydrogen peroxide (1)
- hydrogen phosphate (1)
- image reconstruction (1)
- immunology (1)
- in vivo selection (1)
- industrial catalysis (1)
- industrielle Biokatalyse (1)
- infection (1)
- influenza A virus (1)
- inhibition (1)
- insulin-producing cells (1)
- integrin αIIbβ3 (1)
- intestinal (1)
- isolated sulfite oxidase deficiency (iSOD) (1)
- kINPen (1)
- ketoreductase (1)
- kinases (1)
- kinetics (1)
- laminarin (1)
- lead structure (1)
- lipase (1)
- lipid mediators (1)
- lipid monolayers (1)
- lipids (1)
- liposomes (1)
- liquid-liquid extraction (1)
- liver regeneration (1)
- luciferase (1)
- lysine acetylation (1)
- lysine acetyltransferases (1)
- lysine deacetylases (1)
- mQTL (1)
- magnetic moment (1)
- marine fungi (1)
- marine polysaccharides (1)
- mass spectrometry (1)
- medicinal leeches (1)
- membrane protein (1)
- menaquinones (1)
- metabolite (1)
- metabolites (1)
- metadynamics (1)
- methyltransferases (1)
- microglia (1)
- microorganisms (1)
- mitochondria (1)
- mixed-valence complex (1)
- molybdenum cofactor deficiency (MoCoD) (1)
- molybdopterin (1)
- monooxygenase (1)
- monoterpene acylation (1)
- n/a (1)
- neutral genetic drift (1)
- nitrosative stress (1)
- non-identical reversible reaction (1)
- nucleophilic substitution (1)
- oil (1)
- oligonucleotide conjugate (1)
- oligonucleotides (1)
- optically active dithiolene (1)
- organic synthesis (1)
- overflow metabolites (1)
- oxidation (1)
- oxidative and nitrosative stress (1)
- oxidative post-translational modifications (1)
- oxidative stress (1)
- oxidized lipids (1)
- oxylipins (1)
- pH electrode (1)
- pH-Elektrode (1)
- pH-assay (1)
- phosphorylation (1)
- phosphotransferase system (1)
- pig liver esterase (1)
- pig model (1)
- plasma liquid chemistry (1)
- plasma medicine (1)
- plastic pollution (1)
- platinum deposition on gold (1)
- polycrystalline gold (1)
- porphyran (1)
- proteasome (1)
- protein interaction (1)
- protein-engineering (1)
- proteindesign (1)
- proteomics (1)
- pseudorabies virus (1)
- pyrrolobenzodiazepine (1)
- pyruvate (1)
- pyruvate kinase (1)
- quinhydrone (1)
- radical polishing (1)
- radical reactions (1)
- radiometric interpolation (1)
- rat hepatocytes (1)
- rational design (1)
- rationales Design (1)
- reactive nitrogen species (1)
- reactive species (1)
- recombinant enzyme (1)
- recombinant expression of proteins (1)
- recombination (1)
- reconstitution (1)
- recycling (1)
- redox signaling (1)
- rekombinante Proteinexpression (1)
- respiratory tract infection (1)
- rheumatoid arthritis (1)
- riboswitch (1)
- ribozymes (1)
- scaffold (1)
- scale up for bulk chemical production (1)
- schwere akute Pankreatitis (1)
- secondary plantmetabolites (1)
- secondary structure (1)
- selection assay (1)
- selection-assay (1)
- self assembled monolayer (1)
- sensors (1)
- sepsis (1)
- septic arthritis (1)
- sirtuin (1)
- social arthropods (1)
- spectral matching (1)
- sphingomyelin (1)
- spinlabel (1)
- steered molecular dynamics (1)
- stereoselectivity (1)
- substituent (1)
- substrate specificity (1)
- sugar conformation (1)
- sugar pucker (1)
- suid herpesvirus (1)
- sulfoxidation (1)
- surface change (1)
- surface modification (1)
- surface treatment (1)
- talin (1)
- temporal fitting (1)
- tertiary alcohol (1)
- tertiärer Alkohole (1)
- tetra-nuclear nickel complex (1)
- tetracycline (1)
- three-phase electrochemistry (1)
- titanium dioxide (1)
- transbilayer lipid (flip-flop) motion (1)
- transcript (1)
- transmembrane pores (1)
- type I IFN response (1)
- ulvan (1)
- upcycling (1)
- ustilagic acid (1)
- viral diagnosis (1)
- virology (1)
- virulence factors (1)
- virus (1)
- virus host interaction (1)
- viruses (1)
- vitamin K2 (1)
- volatile organic compound (1)
- white spot syndrome virus (1)
- whole-cell biocatalysis (1)
- zirkular (1)
- Östrogen-Rezeptor-Modulator (1)
- Östrogene (1)
- Übergangsmetallkomplexe (1)
- β-amino acid (1)
- β-phenylalanine ethyl ester (1)
- ω-hydroxy fatty acid (1)
- ω-transaminase (1)
Institute
- Institut für Chemie und Biochemie (185) (remove)
Publisher
- MDPI (17)
- Wiley (11)
- Frontiers Media S.A. (7)
- John Wiley & Sons, Inc. (3)
Biocatalytic Production of Amino Carbohydrates through Oxidoreductase and Transaminase Cascades
(2019)
Plant-derived carbohydrates are an abundant renewable re- source. Transformation of carbohydrates into new products, in- cluding amine-functionalized building blocks for biomaterials applications, can lower reliance on fossil resources. Herein, bio- catalytic production routes to amino carbohydrates, including oligosaccharides, are demonstrated. In each case, two-step bio- catalysis was performed to functionalize d-galactose-contain- ing carbohydrates by employing the galactose oxidase from Fusarium graminearum or a pyranose dehydrogenase from
Agaricus bisporus followed by the w-transaminase from Chro- mobacterium violaceum (Cvi-w-TA). Formation of 6-amino-6- deoxy-d-galactose, 2-amino-2-deoxy-d-galactose, and 2-amino- 2-deoxy-6-aldo-d-galactose was confirmed by mass spectrome- try. The activity of Cvi-w-TA was highest towards 6-aldo-d-gal- actose, for which the highest yield of 6-amino-6-deoxy-d-galac- tose (67%) was achieved in reactions permitting simultaneous oxidation of d-galactose and transamination of the resulting 6- aldo-d-galactose.
The soluble blood protein beta2-glycoprotein I (beta2GPI; 326 aa, MW: 48 kDa, 5 domains) is one of the most abundant proteins in human serum and exhibits two main conformational states: the circular or closed conformation, where the first domain (DI) is bound to the last domain (DV) of the protein, and the linear or open conformation. The defined physiological function of beta2GPI is still unknown, though several roles in pro- and anticoagulation as well as oxidative stress protection were discovered. The open form is considered to play a crucial role in the systemic autoimmune disease antiphospholipid syndrome (APS), which is an acquired thrombophilia characterized by recurring thrombotic events and pregnancy morbidity. Beta2GPI constitutes the main antigen for APS autoantibodies which are supposed to bind a cryptic epitope within DI after a conformational change from closed to open form. However, the pathophysiological mechanism of APS is poorly understood. Therefore, investigating the structural dynamics of this protein in relation to its antigenicity is of high interest.
Post-translational modifications (PTM) of a target protein often show an impact on the formation of neoantigens, for instance in the autoimmune-mediated diseases type 1 diabetes mellitus, rheumatoid arthritis, or multiple sclerosis. Such modified antigens may lead to immune tolerance breakdown as they are unknown to the immune system, which therefore could mistakes self for non-self proteins. In this thesis, two frequently occurring PTM were introduced to beta2GPI and their impact on the protein conformation was studied by biophysical tools (i.e. atomic force microscopy (AFM) imaging, transmission electron microscopy (TEM) imaging, dynamic light scattering (DLS), and circular dichroism (CD) spectroscopy). In order to examine immunopathophysiological relevance of these PTM, additional insights were gained from ELISA which was used to examine binding of anti-DI autoantibodies purified from the blood of APS patients to the modified beta2GPI species.
A characteristic feature of beta2GPI is the high content of lysine residues. Previously, opening of beta2GPI was found to be triggered by a drastic shift in pH and salt concentration (pH 11.5 and 1.15 M NaCl), which results in reversible uncharging of the lysine residues. The aim of this study was to investigate the beta2GPI conformation after lysine acetylation as a model system, to elucidate the role of lysine residues on the conformational dynamics of this protein, and to examine anti-DI autoantibody binding to both the untreated as well as acetylated species.
A strategy to permanently open up the closed form under physiological conditions by chemical acetylation of lysine residues utilizing the sensitive acetylation agent acetic acid N-hydroxysuccinimide ester (NHS-Ac) was established. Complete and specific lysine acetylation was verified by quantification of primary amines exerting a fluoraldehyde o-phthaldialdehyde (OPA) reagent assay, as well as by native PAGE and western blot analysis with an anti-acetylated lysine antibody. Beta2GPI acetylation revealed a partial opening of beta2GPI molecules. Compared to untreated, i.e. native beta2GPI which exhibited 93% of the molecules in closed and 7% in open form, complete lysine residue acetylation generated 39% of beta2GPI in closed and 61% in open conformation as shown by AFM high-resolution imaging. pH 11.5-treated beta2GPI was used as a reference in the applied methods and revealed 38% of the protein in closed and 62% in open conformation. Thus, a significant shift in beta2GPI conformation occurred upon lysine residue acetylation as well as basic pH-treatment. The data indicate that lysine residue acetylation destabilizes the closed form, leading to a facilitated opening of the structure. The closed conformation might be predominantly stabilized by electrostatic interactions of lysine residues, which potentially control the conformational dynamics of this glycoprotein. ELISA confirmed that anti-DI autoantibodies do not bind to untreated (closed) beta2GPI. Although acetylated beta2GPI was shown to have a substantial portion of open proteins, no binding of anti-DI autoantibodies to the acetylated species was found either. Hence, acetylated lysine residues may disrupt the immunorelevant epitope in DI which prevents antibody binding. This finding reveals a new hint for epitope organization. However, further detailed epitope mapping has to be performed.
Beta2GPI carries two structural disulfide bonds per domain, whereas an additional disulfide bond Cys288/Cys326 is located at the C-terminus of DV near the putative contact interface of DI and DV in the closed conformation. It was previously shown that beta2GPI is a substrate of thiol oxidoreductases, including human thioredoxin-1 (Trx-1) generating different redox states of disulfide bond Cys288/Cys326, which might serve as a scavenger in oxidative stress protection in the blood stream. In APS patients, anti-DI antibody titers as well as an enhanced risk for thrombotic events are associated with an increase in the oxidized state of the protein. Hitherto, no structural study has been performed in order to prove a correlation of the redox state and the conformation of beta2GPI. Therefore, investigations of beta2GPI conformation in different redox states of disulfide bond Cys288/Cys326 were carried out. In addition, binding of anti-DI autoantibodies to the untreated (native) as well as reduced protein should be explored.
At first, cysteine residues of untreated, i.e. native beta2GPI were confirmed to be completely in oxidized state using Ellman’s reagent assay and the absence of binding of a thiol-specific agent. Statistical analyses of AFM images revealed that untreated beta2GPI was mainly in closed conformation (80% in closed and 20% in open conformation) in the respective system. In this study, an optimized protocol for enzymatic reduction of disulfide bond Cys288/Cys326 was established. The agent TCEP was used to reduce human Trx-1, which in turn enzymatically reduced beta2GPI. To block reoxidation of free thiols and to facilitate product analysis, cysteine residues of reduced beta2GPI were subsequently labeled with the sensitive and thiol-specific reagent 3-(N-maleimidopropionyl) biocytin (MPB), which carries a biotin function. During protocol establishment, complete and specific reduction of disulfide bond Cys288/Cys326 was confirmed utilizing SDS-PAGE, streptavidin western blot, mass spectrometry (MS) analyses, and a biotin quantification assay. Protocol improvements constituted a homogenous system with remarkable decrease of unspecifically reduced beta2GPI. Upon beta2GPI reduction, AFM imaging revealed no significant shift in protein conformation (75% in closed and 25% in open conformation). These results were qualitatively confirmed by TEM imaging. Therefore, reduction of beta2GPI disulfide bond Cys288/Cys326 did not result in a major conformational change of the protein. Upon in vitro reduction, the closed form is still the main conformation and a direct correlation of beta2GPI redox state and conformation must be refused. Furthermore, beta2GPI reduction led to a strong and statistically highly significant increase in anti-DI autoantibody binding compared to untreated beta2GPI. Thus, the reduced form might be the antigenic form of the protein. In contrast to previous knowledge, these findings suggest that anti-DI autoantibodies may also bind to the closed conformation under certain conditions. Hypothetically, reduction of beta2GPI could induce a minor structural change in DV that might facilitate the binding of APS autoantibodies.
Overall, this study reveals that PTM of beta2GPI may lead to a critical level of destabilization of the closed conformation (as in the case of acetylated beta2GPI) or significantly increase the binding of APS autoantibodies (as in the case of reduced beta2GPI), both of which could have a large impact on APS disease. However, further investigations are necessary to put these new findings in the context of APS immunopathophysiology.
Haloalkanes are serious environmental pollutants commonly employed as pesticides, herbicides, and chemical warfare agents. Although haloalkane production is performed mostly in the chemical industry, it also occurs naturally, mostly enzymatically (halide methyltransferases and haloperoxidases). Elimination of toxic haloalkanes is very important and using haloalkane dehalogenases is a promising and environmentally friendly way to achieve this.[53] Therefore, assays are needed for detecting dehalogenase activity either to find new enzymes or to generate laboratory-evolved variants. In this thesis, a new assay for dehalogenase activity was developed based on halide detection. In this assay halides, as dehalogenase products, are oxidized under mild conditions using the vanadium-dependent chloroperoxidase from Curvularia inaequalis, forming hypohalous acids that are detected using aminophenyl fluorescein.[53] This new halide oxidation assay is much more sensitive than previously known assays, with detection limits of 20 nM for bromide and 1 μM for chloride and iodide. Validation of the assay was done by comparison to a well-established GC-MS method in terms of determining the specific activities of two dehalogenases towards five common substrates (Figure 5).
The HOX assay was modified for iodide-specific detection by using two other dyes, o-phenylenediamine (OPD) and 3,3′,5,5′-tetramethylbenzidine (TBM), instead of APF. Also, selective bromide detection in the presence of the common contaminant chloride was achieved by using a bromoperoxidase. Since the assay relies on halide detection, it is possible to use it for other halide-producing enzymes (Section 8.1). For example, the TMB-modified version was used for screening of halide methyltransferase libraries towards various alkyl iodides.[166] Furthermore, the HOX assay was used to identify promiscuous dehalogenase activity of the epoxide hydrolase CorEH from Corynebacterium sp. C12.[105]
Moreover, studies showed that the HOX assay could be used with in-vitro synthesized protein. Selected dehalogenases, DhlA, DhaA, and DmmA, were synthesized in vitro and used in the assay; the product formation was also validated using GC-MS. In conclusion, the HOX assay can be used with purified protein, whole cells, or in vitro synthesized proteins.
The HOX assay application in microfluidic droplets was investigated since an ultra-high-throughput assay for haloalkane dehalogenases is needed. This investigation showed no leakage of reaction components and products in the short term (~24 h), based on tests done on water-in-oil droplets generated by microfluidic chips. Even though 20 μM droplets were not working, 70 μM droplets were successful for assay implementation. Since the Damborsky group in Brno (CZ) and the deMello group in Zürich (CH), have large dehalogenase libraries and more experience in microfluidics, respectively, we collaborated with these groups to finalize implementation of the assay in an ultrahigh-throughput format. Since the studies are ongoing, final results could not yet be shown in this thesis. However, it can be noted that the issue with 20 μm droplets has been sorted out since our collaborators in Brno noticed that the low fluorescence of the droplets is actually caused by excessive accumulation of fluorescein, which is self-quenching, resulting in low fluorescence once the concentration exceeds 1 μM. By lowering the APF concentration they could optimize the maximum amount of fluorescein formed, and a mutant library has now been successfully screened by our collaborators at the ETH. The last topic of the thesis was an investigation of converting an epoxide hydrolase into a haloalkane dehalogenase. These studies focused on increasing the minor dehalogenase activity of two previously identified epoxide hydrolase (Cif) variants. These Cif variants hardly led to soluble proteins, the PROSS algorithm was used to increase soluble expression. New variants of Cif were generated using a 3DM analysis and the PROSS[164] design. The activities of these variants were determined with the newly developed HOX assay in a whole-cell format. Cif23 E153N-H269D and the PROSS D7 E153N-H269D variant, were found being active against 1,2-dibromoethane. Since the determination of enzyme concentration was hard to measure due to the expression/purification problem, specific activities could not be determined. To solve this problem, a HiBiT-tag was added to the selected variants for determining soluble expression. However, the planned studies could not be completed because of a lack of time and will form the basis for a future study.
This thesis focuses on the establishment of biocatalytic cascade reactions for the production and detection of industrially relevant flavor and fragrance compounds for food and cosmetic products. To meet the consumer’s demand for those products to be natural, environmentally friendly biocatalytic manufacturing processes that operate GMO-free must be established. Thus, this thesis presents such pathways for the production of an industrially relevant long-chain hydroxy fatty acid and the important flavor and aroma compound raspberry ketone. Furthermore, a biosensor for aldehyde detection was implemented to facilitate screening for suitable biocatalysts that produce industrially relevant aldehydes that are widely applied in the flavor and fragrance industry.
The development of the two main types of diabetes mellitus, type 1 and type 2 (T1D, T2D), is closely associated with the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in insulin-secreting pancreatic β-cells. In T1D, β-cell death
is triggered by proinflammatory cytokines, which mainly lead to the formation of ROS
in mitochondria and RNS in the cytosol. Pancreatic β-cells are extraordinarily sensitive
to oxidative stress due to their low glutathione peroxidase and catalase expression.
Thus, hydrogen peroxide (H2O2) cannot be detoxified, neither sufficiently, nor rapidly.
H2O2 itself is a rather weakly reactive ROS but can react in the Fenton reaction to form
highly reactive hydroxyl radicals (●OH), that can damage cells in a variety of ways and
induce cell death. The cell and its organelles are bounded by biological membranes
that differ in their permeability to H2O2. Aquaporins (AQPs) are water-transporting
transmembrane proteins, and some isoforms have been shown to facilitate a bidirectional transport of H2O2 across cellular membranes in addition to water. The role of
AQP8 was investigated in an insulin-producing cell model by stably overexpressing
AQP8 (AQP8↑) and by a CRISPR/Cas9-mediated AQP8 knockout. However, AQP8
proved to be an essential protein for the viability of the insulin-producing RINm5F cells, and so we established a tet-on-regulated AQP8 knockdown (AQP8 KD). Our results highlight that AQP8 is involved in H2O2 transport across the plasma and mitochondrial membranes, and that AQP8 expression gets upregulated by proinflammatory cytokines (in vitro) and in an acutely diabetic rat model (in vivo). Furthermore, it was shown that the increased proinflammatory cytokine toxicity is due to enhanced mitochondrial oxidative stress, because H2O2 cannot be efficiently transported in AQP8 KD cells and ●OH
are increasingly generated. Caspase activity then raises, and apoptosis is increasingly
induced coupled with a proportion of ferroptosis-mediated cell death because of a concomitant decrease in nitric oxide (NO●) concentration. In conclusion, AQP8 is localized in the plasma and mitochondrial membrane of insulin-producing RINm5F cells, where it is involved in H2O2 transport. In T1D, AQP8 plays an important role in the transport of H2O2 from the mitochondrial matrix to the cytosol so that the concentration is lowered in the mitochondria. This wider distribution of H2O2 may ease the inactivation of H2O2.
Ac(et)ylation is a post-translational modification present in all domains of life. First identified in mammals in histones to regulate RNA synthesis, today it is known that is regulates fundamental cellular processes also in bacteria: transcription, translation, metabolism, cell motility. Ac(et)ylation can occur at the ε-amino group of lysine side chains or at the α-amino group of a protein. Furthermore small molecules such as polyamines and antibiotics can be acetylated and deacetylated enzymatically at amino groups. While much research focused on N-(ε)-ac(et)ylation of lysine side chains, much less is known about the occurrence, the regulation and the physiological roles on N-(α)-ac(et)ylation of protein amino termini in bacteria. Lysine ac(et)ylation was shown to affect protein function by various mechanisms ranging from quenching of the positive charge, increasing the lysine side chains’ size affecting the protein surface complementarity, increasing the hydrophobicity and by interfering with other post-translational modifications. While N-(ε)-lysine ac(et)ylation was shown to be reversible, dynamically regulated by lysine acetyltransferases and lysine deacetylases, for N-(α)-ac(et)ylation only N-terminal acetyltransferases were identified and so far no deacetylases were discovered neither in bacteria nor in mammals. To this end, N-terminal ac(et)ylation is regarded as being irreversible. Besides enzymatic ac(et)ylation, recent data showed that ac(et)ylation of lysine side chains and of the proteins N-termini can also occur non-enzymatically by the high-energy molecules acetyl-coenzyme A and acetyl-phosphate. Acetyl-phosphate is supposed to be the key molecule that drives non-enzymatic ac(et)ylation in bacteria. Non-enzymatic ac(et)ylation can occur site-specifically with both, the protein primary sequence and the three dimensional structure affecting its efficiency. Ac(et)ylation is tightly controlled by the cellular metabolic state as acetyltransferases use ac(et)yl-CoA as donor molecule for the ac(et)ylation and sirtuin deacetylases use NAD+ as co-substrate for the deac(et)ylation. Moreover, the accumulation of ac(et)yl-CoA and acetyl-phosphate is dependent on the cellular metabolic state. This constitutes a feedback control mechanism as activities of many metabolic enzymes were shown to be regulated by lysine ac(et)ylation. Our knowledge on lysine ac(et)ylation significantly increased in the last decade predominantly due to the huge methodological advances that were made in fields such as mass-spectrometry, structural biology and synthetic biology. This also includes the identification of additional acylations occurring on lysine side chains with supposedly different regulatory potential. This review highlights recent advances in the research field. Our knowledge on enzymatic regulation of lysine ac(et)ylation will be summarized with a special focus on structural and mechanistic characterization of the enzymes, the mechanisms underlying non-enzymatic/chemical ac(et)ylation are explained, recent technological progress in the field are presented and selected examples highlighting the important physiological roles of lysine ac(et)ylation are summarized.
Die akute Pankreatitis ist durch eine vorzeitige Aktivierung von Verdauungsenzymen noch innerhalb der Azinuszellen gekennzeichnet. Die lysosomale Hydrolase Cathepsin B (CTSB) spielt hierbei eine entscheidende Rolle, indem sie Trypsinogen zu Trypsin aktiviert. Für die Trypsinogenaktivierung durch CTSB ist eine Co-Lokalisierung beider Enzyme innerhalb desselben subzellulären Kompartiments erforderlich. Ziel dieser Arbeit war es, die Regulation der CTSB-Aktivität durch den Cysteinprotease-Inhibitor Cystatin C im Verlauf der akuten und chronischen Pankreatitis näher zu untersuchen.
Subzelluläre Fraktionierungsexperimente zeigten eine deutliche Lokalisation von Cystatin C und aktiven Cathepsin B im sekretorischen Kompartiment muriner Azinuszellen. Immunofluoreszenzfärbungen zeigten ebenfalls, dass Cystatin C zusammen mit der pankreatischen Amylase im sekretorischen Kompartiment von Azinuszellen lokalisiert ist. Auch in humanen Probenmaterial konnten wir zeigen, dass Cystatin C im sekretorischen Kompartiment lokalisiert ist und auch sekretiert wird. Experimente mit rekombinanten Proteinen zeigten eine deutliche pH-abhängige inhibitorische Wirkung von Cystatin C auf Cathepsin B. Unter sauren pH Bedingungen dimerisiert Cystatin C und ist somit nicht mehr in der Lage die Aktivität von CTSB zu inhibieren. Weiterhin konnten wir zeigen, dass aktives Trypsin Cystatin C prozessiert. Bei dieser Spaltung entsteht ein Cystatin C-Fragment, welches nicht mehr in der Lage ist, CTSB zu inhibieren, sondern vielmehr die auto-inhibitorische Kapazität von Cathepsin B unterbindet und somit die Aktivität stabilisiert. Neben Cystatin C wird in Azinuszellen auch Cystatin B exprimiert, ein weiterer Inhibitor der Cystein-Proteasen. Im Gegensatz zu Cystatin C ist Cystatin B exklusiv im cytosolischen Kompartiment der Azinuszelle lokalisiert. Dies ist wahrscheinlich ein Schutzmechanismus, welcher die Zelle vor einer cytosolischen Cathepsin-Aktivität schützen soll. Die genetische Deletion von Cystatin C im Mausmodell der akuten Pankreatitis führte zu einer erhöhten Aktivität sekretorischer Proteasen in Azinuszellen, sowie im Gesamthomogenat und in subzellulären Fraktionen. Dementsprechend zeigte sich auch ein deutlich erhöhter Schweregrad in der akuten und chronischen Pankreatitis.
Unsere Experimente lassen vermuten, dass die Aktivität von Cathepsin B unter physiologischen Bedingungen durch Cystatin C unterbunden wird, um so eine verfrühte Aktivierung des Trypsinogens zu verhindern. Im Verlauf der Pankreatitis wird dieser protektive Mechanismus jedoch überwunden. Die Aktivität von Cathepsin B steigt deutlich in der schweren Zymogengranula-Fraktion an, trotz der Präsenz von Cystatin C.
Zusammenfassend lassen unsere Ergebnisse vermuten, dass prozessiertes (aktives) Cathepsin B selbst unter physiologischen Bedingungen im sekretorischen Kompartiment von Azinuszellen bereits vorhanden ist. Seine Aktivität wird dort durch Cystatin C inhibiert, wodurch eine vorzeitige, durch CTSB induzierte Trypsinogenaktivierung verhindert wird. Die Ansäuerung der sekretorischen Vesikel, wie bei der Pankreatitis, verringert die CTSB-Hemmung durch Cystatin C, während es gleichzeitig zu einer Cystatin C-Degradation durch Trypsin kommt. Dies ermöglicht eine verlängerte und pH-unempfindliche Protease-Aktivierung über CTSB in der Anfangsphase der Pankreatitis. Cystatin C spielt somit eine wesentliche Rolle für die Regulation der CTSB-Aktivität im sekretorischen Kompartiment von Azinuszellen und stellt damit einen entscheidenden pathophysiologisch relevanten Mechanismus für die akute und chronische Pankreatitis dar.