- E-postKnut.Teigen@uib.no
- Telefon+47 55 58 63 28
- BesøksadresseJonas Lies vei 915009 Bergen
- PostadressePostboks 78045020 Bergen
Jeg er professor ved Institutt for biomedisin ved Universitetet i Bergen, og en av flere gruppeleder i Metabolisme og kreft-gruppen. Forskningen i vår gruppe har som mål å forstå molekylære interaksjoner på atomnivå og de nyanserte sammenhengene mellom struktur, dynamikk og funksjon av biomolekyler. Vi utvikler og anvender beregningsmetoder for å simulere molekylære bevegelser, som supplerer eksperimentelle observasjoner.
Gjennom samarbeid med grupper som utvikler Amber-programvaren for molekylære simuleringer, har vi utviklet Amber-kraftfeltet for å simulere molekylære interaksjoner i lipidkomplekser. Med Amber programvaren er vi nå i stand til å simulere komplekse molekylære systemer av hvilken som helst sammensetning. Vi anvender disse metodene for å forstå funksjonen til store molekylære systemer basert på intermolekylære krefter og iboende dynamikk.
Vår kraftfeltutvikling er også relevant for metoder for virtuell screening, der vi ønsker å finne små molekyler med potensiale til å utvikles til et medikament. Den virtuelle screeningen integreres med eksperimentell screening av små forbindelser utført av andre grupper ved Institutt for Biomedisin.
Jeg er medgründer og aksjonær i selskapet Pluvia Pharma AS, et oppstarts-biotec firma i Bergen som har som mål å utvikle molekyler med potensiale for å korrigere medfødte arvelige sykdommer som skyldes misfolding av proteiner.
Jeg er semesterstyreleder og har ansvar for innholdet i andre semester på medisinstudiet i Bergen og er medlem av Programutvalget i Medisin ved UiB. Jeg underviser i basalfagene for farmasi, tannlege og medisin og har i tillegg undervisning om strukturbiologi på master- og phd-emner ved instituttet. Jeg tilbyr masteroppgaver for studenter i farmasi, nanovitenskap, biomedisin og medisinsk teknologi i tillegg til prosjekter for forskerlinjen på medisin. Gjennom FEBS (Federation of European Biochemical Societies) er jeg involvert i utvikling av biokjemi-undervisning og deltar i FEBS-fora som Norges ambassadør for biokjemi-undervisning.
Når jeg ikke underviser i biokjemi, har jeg en lidenskap for ski og skikjøring. Som medlem av utdanningskomiteen i Den Norske Skiskole bidrar jeg med opplæring og internasjonal ISIA sertifisering av skilærere i Norge.
Vitenskapelig artikkel
- (2022). Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation. Nature Communications.
- (2022). Modeling of mutant superoxide dismutase 1 octamers with cross-linked disulfide bonds. Journal of Molecular Modeling. 1-7.
- (2022). Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone. Communications Biology. 1-14.
- (2021). Synthetic corticosteroids as tryptophan hydroxylase stabilizers. Future Medicinal Chemistry. 1465-1474.
- (2021). Investigating the Disordered and Membrane-Active Peptide A-Cage-C Using Conformational Ensembles. Molecules. 3607.
- (2020). The Arabidopsis (ASHH2) CW domain binds monomethylated K4 of the histone H3 tail through conformational selection. The FEBS Journal. 4458-4480.
- (2020). Levalbuterol lowers the feedback inhibition by dopamine and delays misfolding and aggregation in tyrosine hydroxylase. Biochimie.
- (2020). Inhibition of Tryptophan Hydroxylases and Monoamine Oxidase-A by the Proton Pump Inhibitor, Omeprazole—In Vitro and In Vivo Investigations. Frontiers in Pharmacology.
- (2020). Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer. Cancer Research. 2163-2174.
- (2020). Discovery and biological characterization of a novel scaffold for potent inhibitors of peripheral serotonin synthesis. Future Medicinal Chemistry. 1461-1474.
- (2019). Dominant ARL3-related retinitis pigmentosa. Ophthalmic Genetics. 124-128.
- (2019). Characterization of the interaction of the antifungal and cytotoxic cyclic glycolipopeptide hassallidin with sterol-containing lipid membranes. Biochimica et Biophysica Acta - Biomembranes. 1510-1521.
- (2017). Substituting Tyr138 in the active site loop of human phenylalanine hydroxylase affects catalysis and substrate activation. FEBS Open Bio. 1026-1036.
- (2017). Cripto stabilizes GRP78 on the cell membrane. Protein Science. 653-661.
- (2016). Simulation of lipid bilayer self-assembly using all-atom lipid force fields. Physical Chemistry, Chemical Physics - PCCP. 10573-10584.
- (2015). Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression. Neurochemistry International. 173-184.
- (2015). Discovery of compounds that protect tyrosine hydroxylase activity through different mechanisms. Biochimica et Biophysica Acta - Proteins and Proteomics. 1078-1089.
- (2015). All-atom lipid bilayer self-assembly with the AMBER and CHARMM lipid force fields. Chemical Communications. 4402-4405.
- (2014). The N-terminal sequence of tyrosine hydroxylase is a conformationally versatile motif that binds 14-3-3 proteins and membranes. Journal of Molecular Biology (JMB). 150-168.
- (2014). Lipid14: The amber lipid force field. Journal of Chemical Theory and Computation. 865-879.
- (2014). Introduction of aromatic ring-containing substituents in cyclic nucleotides is associated with inhibition of toxin uptake by the hepatocyte transporters OATP 1B1 and 1B3. PLOS ONE.
- (2013). Screening and evaluation of small organic molecules as ClpB inhibitors and potential antimicrobials. Journal of Medicinal Chemistry. 7177-7189.
- (2013). Iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from streptosporangium sp. induces apoptosis selectively in myeloid leukemia cell lines and patient cells. Marine Drugs. 332-349.
- (2013). Inhibition of sorbitol dehydrogenase by nucleosides and nucleotides. Biochemical and Biophysical Research Communications - BBRC. 202-208.
- (2012). LIPID11: A modular framework for lipid simulations using amber. Journal of Physical Chemistry B. 11124-11136.
- (2011). The regulatory subunit of PKA-I remains partially structured and undergoes beta-aggregation upon thermal denaturation. PLOS ONE. 10 sider.
- (2011). Substrate Hydroxylation by the Oxido-Iron Intermediate in Aromatic Amino Acid Hydroxylases: A DFT Mechanistic Study. European Journal of Inorganic Chemistry (EurJIC). 2720-2732.
- (2011). Intramolecular hydrogen bonding in articaine can be related to superior bone tissue penetration: A molecular dynamics study. Biophysical Chemistry. 18-25.
- (2011). Formation of the Iron-Oxo Hydroxylating Species in the Catalytic Cycle of Aromatic Amino Acid Hydroxylases. Chemistry - A European Journal. 3746-3758.
- (2011). Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations. PLoS Computational Biology.
- (2011). Binding of ATP at the active site of human pancreatic glucokinase - nucleotide-induced conformational changes with possible implications for its kinetic cooperativity. The FEBS Journal. 2372-2386.
- (2010). Superstoichiometric binding of L-Phe to phenylalanine hydroxylase from Caenorhabditis elegans: evolutionary implications. Amino Acids. 1463-1475.
- (2009). Overview of computational methods employed in early-stage drug discovery. Future Medicinal Chemistry. 49-63.
- (2009). Evolution of regulation, structure and function in phenylalanine hydroxylase. Pteridines. 42-50.
- (2007). A simple method to calculate the accessible volume of protein-bound ligands: Application for ligand selectivity. Journal of Molecular Graphics and Modelling. 429-433.
- (2006). Specific interaction of the diastereomers 7(R)- and 7(S)-tetrahydrobiopterin with phenylalanine hydroxylase: implications for understanding primapterinuria and vitiligo. The FASEB Journal. 2130-2132.
- (2006). Epac1 and cAMP-dependent protein kinase holoenzyme have similar cAMP affinity, but their cAMP domains have distinct structural features and cyclic nucleotide recognition. Journal of Biological Chemistry. 21500-21511.
- (2005). The reaction mechanism of phenylalanine hydroxylase. A question of coordination. Pteridines. 27-34.
- (2004). Thermodynamic characterization of the binding of tetrahydropterins to phenylalanine hydroxylase . Journal of the American Chemical Society. 13670-13678.
- (2004). Tetrahydrobiopterin binding to aromatic amino acid hydroxylases. Ligand recognition and specificity. Journal of Medicinal Chemistry. 5962-5971.
- (2004). Structural and stability effects of phosphorylation � Localized structural changes in phenylalanine hydroxylase. Protein Science. 1219-1226.
- (1999). The structural basis of the recognition of phenylalanine and pterin cofactors by phenylalanine hydroxylase. Implications for the catalytic mechanism. Journal of Molecular Biology (JMB). 807-823.
- (1999). The structural Basis of the Recognition of Phenylalanine and Pterine Cofactors by Phenylalanine Hydroxylase. Implications for the Catalytic Mechanism. Journal of Molecular Biology (JMB). 807-823.
Vitenskapelig foredrag
- (2009). Dioxygen in aromatic amino acid hydroxylases.
- (1998). NMR study on the conformation of L-phenylalanine and dihydrobiopterin bound to wild-type and mutant forms of recombinant human phenylalanine hydroxylase.
Short communication
- (2010). Water dissociation and dioxygen binding in phenylalanine hydroxylase. European Journal of Inorganic Chemistry (EurJIC). 351-356.
Mastergradsoppgave
- (2016). Characterization of prevalent phenylketonuria mutations Effect of potential pharmacological chaperones .
- (2015). Identification of small molecular modulators of 14-3-3 functions. A virtual screening approach with experimental validation.
- (2015). Discovery of small-molecular disruptors of protein-protein inteactions A virtual screening approach applied to 14-3-3¿ and tyrosine hydroxylase.
- (2014). Identification of pharmacological chaperones for Phenylalanine Hydroxylase A virtual screening approach to discover novel drug candidates for treatment of phenylketonuria.
- (2014). IDENTIFICATION OF INHIBITORS OF TRYPTOPHAN HYDROXYLASE 1.
- (2012). Stabilisation of Tyrosine Hydroxylase in Nanoparticles for Enzyme Replacement Therapy.
- (2012). SEARCH AND ANALYSIS OF COMPOUNDS THAT STABILIZE TYROSINE HYDROXYLASE - IDENTIFICATION OF PHARMACOLOGICAL CHAPERONES.
- (2011). Interactions between polychlorinated biphenyls (PCBs) and a phospholipid bilayer: A molecular dynamics study.
- (2008). INTERACTION OF A LOCAL ANAESTHETIC WITH MEMBRANE LIPIDS STUDIED COMPUTER MODELLING.
- (2008). BIOLOGICAL TARGETS OF LOCAL ANAESTHETICS – A MOLECULAR MODELLING STUDY.
Doktorgradsavhandling
- (2015). A study of Structure-Function-Stability Relationships in Tyrosine Hydroxylase.
- (2004). Structural and Functional Aspects of Pterin-Binding Enzymes - A Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling Study.
Vitenskapelig Kapittel/Artikkel/Konferanseartikkel
- (2014). Structure–Function Relationships in the Aromatic Amino Acid Hydroxylases Enzyme Family: Evolutionary Insights.
- (2010). The aromatic amino acid hydroxylase mechanism: a perspective from computational chemistry. 64 sider.
Sammendrag/abstract
- (2012). Developing a comprehensive modular phospholipid force field for AMBER. Abstract of Papers of the American Chemical Society. 1 sider.
- (2012). AMBER-Lipid 11: A new modular lipid force field for molecular dynamics. Abstract of Papers of the American Chemical Society. 1 sider.
Poster
- (2022). High-throughput screening for VMAT2 activity modulators.
- (2020). Searching for new inhibitors of vesicular monoamine transporter 2 by differential scanning fluorimetry.
- (2020). Identification of VMAT2 inhibitory compounds.
- (2010). Dioxygen Binding and Formation of the Hydroxylating FeIV=O Intermediate in Aromatic Amino Acid Hydroxylases.
- (2010). Can intramolecular hydrogen bonding in articaine be related to superior bone tissue penetration? A molecular dynamics study.
- (2009). Molecular dynamics simulation: Interaction between the local anaesthetic articaine and membrane models.
- (2009). Catalytic cycle of phenylalanine hydroxylase.
- (2009). Catalytic cycle of phenylalanine hydroxylase.
- (2008). Interactions between the local anesthetic articaine and membranes: A theoretical and experiemntal study.
- (2008). Interaction of a local anaesthetic with lipid membranes studied by computer modelling.
- (2008). Drug-membrane interactions. An explanation for the anti-inflammatory effect of local anesthetics?
Errata
- (2016). Erratum: Discovery of compounds that protect tyrosine hydroxylase activity through different mechanisms (Biochimica et Biophysica Acta - Proteins and Proteomics (2015) 1854:9 (1078-1089) DOI: 10.1016/j.bbapap.2015.04.030). Biochimica et Biophysica Acta - Proteins and Proteomics. 317.
Vitenskapelig oversiktsartikkel/review
- (2016). Pharmacological chaperones that protect Tetrahydrobiopterin dependent aromatic amino acid hydroxylases through different mechanisms. Current Drug Targets. 1515-1526.
- (2010). The aromatic amino acid hydroxylase mechanism: A perspective from computational chemistry. Advances in Inorganic Chemistry. 437-500.
- (2009). Rescuing proteins of low kinetic stability by chaperones and natural ligands; phenylketonuria, a case study. Progress in Nucleic Acid Research and Molecular Biology. 89-134.
- (2007). Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. Current Medicinal Chemistry. 455-467.