Blar i forfatter "Lund, Bjarte Aarmo"
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2-Pyridinyl/quinolyl-phenylamino-quinoline Complexes With CF3 and C2F5 Ligated Ni
Håheim, Katja Stangeland; Deolka, Shubham; Fayzullin, Robert; Lund, Bjarte Aarmo; Khaskin, Eugene; Sydnes, Magne Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2024-06-21)A new ligand architecture based on quinoline/pyridine attached ortho to the amine functionality on an aniline, which is coupled to another quinoline unit has been prepared. Ligands <b>L1</b> and <b>L2</b> have been complexed with CF<sub>3</sub> and C<sub>2</sub>F<sub>5</sub> ligated nickel centers. The resulting complexes have been extensively studied by NMR spectroscopy (on <sup>1</sup>H, ... -
Accurate Computation of Thermodynamic Activation Parameters in the Chorismate Mutase Reaction from Empirical Valence Bond Simulations
Wilkins, Ryan Scott; Lund, Bjarte Aarmo; Isaksen, Geir Villy; Åqvist, Johan Lennart Gösta; Brandsdal, Bjørn Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-19)Chorismate mutase (CM) enzymes have long served as model systems for benchmarking new methods and tools in computational chemistry. Despite the enzymes’ prominence in the literature, the extent of the roles that activation enthalpy and entropy play in catalyzing the conversion of chorismate to prephenate is still subject to debate. Knowledge of these parameters is a key piece in fully understanding ... -
The Ambivalence of Connexin43 Gap Peptides in Cardioprotection of the Isolated Heart against Ischemic Injury
Falck, Aleksander Tank; Lund, Bjarte Aarmo; Johansen, David; Lund, trine; Ytrehus, Kirsti (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-09-05)The present study investigates infarct-reducing effects of blocking ischemia-induced opening of connexin43 hemichannels using peptides Gap19, Gap26 or Gap27. Cardioprotection by ischemic preconditioning (IPC) and Gap peptides was compared, and combined treatment was tested in isolated, perfused male rat hearts using function and infarct size after global ischemia, high-resolution respirometry of ... -
ASM Microbe 2016
Lund, Bjarte Aarmo (Journal article; Tidsskriftartikkel, 2016-09-12) -
Biochemical and biophysical characterization of the OXA-48-like carbapenemase OXA-436
Lund, Bjarte Aarmo; Thomassen, Ane Molden; Carlsen, Trine Josefine Warg; Leiros, Hanna-Kirsti Schrøder (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-08-31)The crystal structure of the class D β-lactamase OXA-436 was solved to a resolution of 1.80 Å. Higher catalytic rates were found at higher temperatures for the clinically important antibiotic imipenem, indicating better adaptation of OXA-436 to its mesophilic host than OXA-48, which is believed to originate from an environmental source. Furthermore, based on the most populated conformations during ... -
Biotech applications of protein kinase affinity interactions
Lund, Bjarte Aarmo (Master thesis; Mastergradsoppgave, 2013-05)Protein kinases provide one of the cell’s most important methods for signaling and control. 2% of the encoding genome consists of protein kinase genes, and from 10-50% of the proteins in the cell are phosphorylated at some point in the cell cycle. Malfunction of protein kinases is connected to several disease-conditions, most prominently cancer, Alzheimer’s and diabetes. Understanding the ... -
Computational design of the temperature optimum of an enzyme reaction
van der Ent, Florian; Skagseth, Susann; Lund, Bjarte Aarmo; Sočan, Jaka; Griese, Julia J.; Brandsdal, Bjørn Olav; Åqvist, Johan Lennart Gösta (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-28)Cold-adapted enzymes are characterized both by a higher catalytic activity at low temperatures and by having their temperature optimum down-shifted, compared to mesophilic orthologs. In several cases, the optimum does not coincide with the onset of protein melting but reflects some other type of inactivation. In the psychrophilic α-amylase from an Antarctic bacterium, the inactivation is thought to ... -
Conformational tuning improves the stability of spirocyclic nitroxides with long paramagnetic relaxation times
Sowinski, Mateusz; Gahlawat, Sahil; Lund, Bjarte Aarmo; Warnke, Anna-Luisa; Hopmann, Kathrin Helen; Lovett, Janet E.; Haugland, Marius Myreng (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-05)Nitroxides are widely used as probes and polarization transfer agents in spectroscopy and imaging. These applications require high stability towards reducing biological environments, as well as beneficial relaxation properties. While the latter is provided by spirocyclic groups on the nitroxide scaffold, such systems are not in themselves robust under reducing conditions. In this work, we introduce ... -
Cryptic β-Lactamase Evolution Is Driven by Low β-Lactam Concentrations
Fröhlich, Christopher; Gama, João Alves; Harms, Klaus; Hirvonen, Viivi H. A.; Lund, Bjarte Aarmo; van der Kamp, Marc W.; Johnsen, Pål Jarle; Samuelsen, Ørjan; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-28)Our current understanding of how low antibiotic concentrations shape the evolution of contemporary β-lactamases is limited. Using the widespread carbapenemase OXA-48, we tested the long-standing hypothesis that selective compartments with low antibiotic concentrations cause standing genetic diversity that could act as a gateway to developing clinical resistance. Here, we subjected <i>Escherichia ... -
Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D β-Lactamase, OXA-436, Found in Isolates from Four Patients Involving Six Different Hospitals in Denmark.
Samuelsen, Ørjan; Hansen, Frank; Aasnæs, Bettina; Hasman, Henrik; Lund, Bjarte Aarmo; Leiros, Hanna-Kirsti S.; Lilje, Berit; Janice, Jessin; Jakobsen, Lotte; Littauer, Pia; Søes, Lillian M; Holzknecht, Barbara J.; Andersen, Leif P; Stegger, Marc; Andersen, Paal S.; Hammerum, Anette M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-10-23)The diversity of OXA-48-like carbapenemases are continually expanding. In this study, we describe the dissemination and characteristics of a novel class D carbapenemase (CHDL) named OXA-436. In total, six OXA-436-producing Enterobacteriaceae isolates including Enterobacter asburiae (n=3), Citrobacter freundii (n=2) and Klebsiella pneumoniae (n=1) were identified in four patients in the period between ... -
A focused fragment library targeting the antibiotic resistance enzyme - Oxacillinase-48: Synthesis, structural evaluation and inhibitor design
Ahkter, Sundus; Lund, Bjarte Aarmo; Ismael, Aya; Langer, Manuel; Isaksson, Johan; Christopeit, Tony; Leiros, Hanna-Kirsti S.; Bayer, Annette (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-10)β-Lactam antibiotics are of utmost importance when treating bacterial infections in the medical community. However, currently their utility is threatened by the emergence and spread of β-lactam resistance. The most prevalent resistance mechanism to β-lactam antibiotics is expression of β-lactamase enzymes. One way to overcome resistance caused by β-lactamases, is the development of β-lactamase ... -
Fragment-Based Drug Discovery
Lund, Bjarte Aarmo (Journal article; Tidsskriftartikkel, 2015-06-13) -
A high-throughput, restriction-free cloning and screening strategy based on ccdB-gene replacement
Bjerga, Gro Elin Kjæreng; Lund, Bjarte Aarmo; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2014)Background In high-throughput demanding fields, such as biotechnology and structural biology, molecular cloning is an essential tool in obtaining high yields of recombinant protein. Here, we address recently developed restriction-free methods in cloning, and present a more cost-efficient protocol that has been optimized to improve both cloning and clone screening. Results In our case study, ... -
The OXA-class of β-lactamases. A structural view on antibiotic resistance
Lund, Bjarte Aarmo (Doctoral thesis; Doktorgradsavhandling, 2017-09-01)Antibiotic resistance is a topic that concerns everyone, and by 2050 deaths due to antibiotic resistant bacteria may surpass number of deaths due to cancer. The OXA-class of antibiotic resistance enzymes is a formidable threat, but has not received the same attention as other resistance enzymes. The goal of the project was to understand antibiotic resistance enzymes at an atomic scale and to develop ... -
Regiodivergent Synthesis of 11H-Indolo[3,2-c]quinolines and Neocryptolepine from a Common Starting Material
Håheim, Katja Stangeland; Lund, Bjarte Aarmo; Sydnes, Magne Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-02-23)A large number of diversely functionalized analogs of the bioactive natural products neocryptolepine and isocryptolepine have been prepared from a series of 3-bromoquinoline derivatives. The neocryptolepines were obtained by a Pd<sup>0</sup>-catalyzed C−C bond coupling followed by C−N bond formation in yields up to 80 %, whereas the indoloquinolines were prepared by a Suzuki-Miyaura cross-coupling ... -
Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening
Lund, Bjarte Aarmo; Christopeit, Tony; Guttormsen, Yngve; Bayer, Annette; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-05-11)The spread of antibiotic resistant bacteria is a global threat that shakes the foundations of modern healthcare. β-Lactamases are enzymes that confer resistance to β-lactam antibiotics in bacteria, and there is a critical need for new inhibitors of these enzymes for combination therapy together with an antibiotic. With this in mind, we have screened a library of 490 fragments to identify starting ... -
Side-Chain Interactions in d/l Peptide Nanotubes: Studies by Crystallography, NMR Spectroscopy and Molecular Dynamics
Silk, Mitchell Ramesh; Price, Jason R.; Mohanty, Biswaranjan; Leiros, Hanna-Kirsti Schrøder; Lund, Bjarte Aarmo; Thompson, Phillip E.; Chalmers, David (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-08-20)Our understanding of the factors affecting the stability of cyclic d / l peptide (CP) nanotubes remains underdeveloped. In this work, we investigate the impact of side chain alignment, hydrophobicity and charge on CP nanotube stability through X-ray crystallography, NMR spectroscopy and molecular dynamics (MD) simulations. We characterise the distinct CP-CP alignments that can form and identify ... -
Structure and Mechanism of a Cold-Adapted Bacterial Lipase
van der Ent, Florian; Lund, Bjarte Aarmo; Svalberg, Linn; Purg, Miha; Chukwu, Ghislean; Widersten, Mikael; Isaksen, Geir Villy; Brandsdal, Bjørn Olav; Åqvist, Johan Lennart Gösta (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-05-03)The structural origin of enzyme cold-adaptation has been the subject of considerable research efforts in recent years. Comparative studies of orthologous mesophilic–psychrophilic enzyme pairs found in nature are an obvious strategy for solving this problem, but they often suffer from relatively low sequence identity of the enzyme pairs. Small bacterial lipases adapted to distinctly different ... -
Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis
Lund, Bjarte Aarmo; Thomassen, Ane Molden; Carlsen, Trine Josefine Olsen; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2017)The first crystal structures of the class D β-lactamases OXA-181 and OXA-245 were determined to 2.05 and 2.20 Å resolution, respectively; in addition, the structure of a new crystal form of OXA-163 was resolved to 2.07 Å resolution. All of these enzymes are OXA-48-like and have been isolated from different clinical Klebsiella pneumoniae strains and also from other human pathogens such as Pseudomonas ... -
ThermoSlope: A Software for Determining Thermodynamic Parameters from Single Steady-State Experiments
Lund, Bjarte Aarmo; Brandsdal, Bjørn Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-11-26)The determination of the temperature dependence of enzyme catalysis has traditionally been a labourious undertaking. We have developed a new approach to the classical Arrhenius parameter estimation by fitting the change in velocity under a gradual change in temperature. The evaluation with a simulated dataset shows that the approach is valid. The approach is demonstrated as a useful tool by ...