Structure and Function of Metabolic Enzymes

Structure and Function of Metabolic Enzymes

Structure and Function of Metabolic Enzymes

Enzymes and enzyme complexes are the key actors in all metabolic transformations and the modification and alteration of their function underlies the majority of all therapeutical approaches. They act as structural components of the cell, as components of complex signalling pathways and in molecular recognition. They transfer electrons and ions, conserve and convert energy and function as catalysts to mediate the chemical reactions required for the operation of a living cell with unmatched efficiency. Freiburg Metabolism researchers study the biochemical and biophysical properties of metabolic enzymes to understand their structure and dynamics and their interaction within the cell. The community is moving from static pictures of enzyme action to the dynamic properties and thus determine the functionality of an enzyme as a biological catalyst for all cellular processes.

Luciana Hannibal ORCiD

Faculty of Medicine and Medical Center – Department of General Pediatrics, Adolescent Medicine and Neonatology, MetaboCF Core Facility

RESEARCH: Inborn errors of metabolism, Genetic modifiers of metabolism, Sulfur-metabolism, Redox signalling, Cofactor enzymology and trafficking, Nutrition, Nutritional and Genetic deficiencies of vitamin B12, multiorgan-metabolic integration

METHODS: Metabolic labeling in cell culture, Targeted metabolomic profiling by mass spectrometry, Characterization of pathogenic protein variants, Protein-cofactor interactions, Rapid kinetics by stopped-flow, Biomarker discovery and standardization

TECHNOLOGIES: UHPLC Nexera X2/QTRAP Sciex 6500+ MS, HPLC -TSQ Vantage Triple Quadrupole MS, GC-MS system (7890 GC system coupled to a 5975C mass spectrometer, Agilent), Stopped-Flow with double mixer and dual UV-Vis/Fluorescence detection

Oliver Einsle ORCiD

Faculty of Chemistry and Pharmacy – Institute of Biochemistry

RESEARCH: Structure and Function of Metabolic Enzymes, , Refactoring of Metabolic Pathways Enzymology, Bioinorganic Chemistry, Structural Biology, Assembly and Biogenesis of Enzymes and Enzyme Complexes

METHODS: Microbiology, Oxic and Anoxic Protein Biochemistry, UV/vis Spectroscopy, EPR Spectroscopy, RT-PCR, Isothermal Titration Calorimetry, Analytical Size-Exclusion Chromatography, Molecular Modelling, Cryo-EM, X-ray Crystallography

TECHNOLOGIES: EPR Sprectrometer (Bruker ElexSys 500), X-ray diffractometer (Rigaku), Cryo-EM (Thermo Fisher)

Susana Andrade ORCiD

Faculty of Chemistry and Pharmacy – Institute for Biochemistry

RESEARCH: Metabolite signaling, Metabolite transport, Structure and function of Proteins, Channels, Transporters, Receptors, (Metallo-) Enzymes, Transport mechanisms, Receptor activation, Signal transduction, Protein-protein interaction

METHODS: Protein engineering and isolation, Affinity and size-exclusion chromatography, Molecular Biology, X-ray crystallography, cryo-EM, Proteoliposomes, Lipids, Detergents, Nanoparticles, SSM-/PLB-Electrophysiology, Microscale thermophoresis, Stopped-flow kinetics

TECHNOLOGIES: Planar Lipid Bilayer Electrophysiology (Warner Instr.), Solid-Supported Membrane Electrophysiology (Nanion Tech.), SX-20 Stopped Flow Spectrometer (Applied Photophysics)

Anna Köttgen ORCiD

Faculty of Medicine and Medical Center – Institute of Genetic Epidemiology

RESEARCH: Genetic determinants of Metabolite Levels, Metabolite Transport Proteins, Metabolite handling in Kidney, Inborn Errors of Metabolism, Complex metabolic Diseases, Pharmaco-metabolomics

METHODS: Population-scale genetic screens, whole-exome sequencing, multi-Omics data integration (e.g., metabolomics and genomics), non-targeted metabolomics by MS, statistical data analysis of (non-)targeted MS and NMR metabolomics, pathway analysis

Jennifer Andexer ORCiD

Faculty of Chemistry and Pharmacy – Institute of Pharmaceutical Sciences

RESEARCH: Biomimetic Metabolic Pathways, Metabolic Engineering, Multi-enzyme cascades, Biocatalysis, Enzyme Catalysis

METHODS: Genetic Manipulation of Metabolism, Heterologous Expression, Analysis via HPLC and LC-MS

TECHNOLOGIES: HPLC (DAD & ELSD)

Thorsten Friedrich ORCiD

Faculty of Chemistry and Pharmacy – Institute of Biochemistry

RESEARCH: Biochemistry, Respiration, Energy Conversion, Enzyme Complexes of Respiration: Structure/Function, Biogenesis and Inhibitors, (Ubi)Quinone Chemistry, Reactive Oxygen Species, Structural Biology, Iron-Sulphur clusters, Mitochondria, Bacteria

METHODS: Genetic Manipulation of Microorganisms, Purification of Membrane Proteins, Protein Stability, Inhibitor screening, Protein labeling (EPR-, fluorescent- and IR-probes), Liposome techniques, He-temp. EPR-spectroscopy, Cryo-EM (via collaboration)

TECHNOLOGIES: 10L Fermenter (Bioengineering), Äkta Protein Purification Systems (GE Healthcare), He-temp. X-Band EPR (Bruker), Fluorescence DSC (PerkinElmer), Fluorescence Imaging (Vilber), Oxygen Electrode (HansaTech), Protein Electrochemistry (ProSense)

GRK 1976, GRK 2202, SPP 1927, DFDK 0407