A5037225529- Protein Structure and Dynamics
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Advanced NMR Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- Protease and Inhibitor Mechanisms
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- NMR spectroscopy and applications
- Bioinformatics and Genomic Networks
- Bacteriophages and microbial interactions
- Machine Learning in Bioinformatics
- Supramolecular Self-Assembly in Materials
- Solid-state spectroscopy and crystallography
- Molecular spectroscopy and chirality
- Alzheimer's disease research and treatments
- Neuroendocrine regulation and behavior
- Psoriasis: Treatment and Pathogenesis
- Adenosine and Purinergic Signaling
- Glycosylation and Glycoproteins Research
- RNA regulation and disease
Aarhus University
2013-2024
Aarhus University Hospital
2015-2017
Massey University
2010
University of Southern Denmark
2003-2009
Abstract The fibril structure formed by the amyloidogenic fragment SNNFGAILSS of human islet amyloid polypeptide (hIAPP) is determined with 0.52 Å resolution. Symmetry information contained in easily obtainable resonance assignments from solid‐state NMR spectra (see picture), along long‐range constraints, can be applied to uniquely identify supramolecular organization fibrils. magnified image
Uncontrolled misfolding of proteins leading to the formation amyloid deposits is associated with more than 40 types diseases, such as neurodegenerative diseases and type-2 diabetes. These irreversible fibrils typically assemble in distinct stages. Transitions among various intermediate stages are subject many studies but not yet fully elucidated. Here, we combine high-resolution atomic force microscopy quantitative nanomechanical mapping determine self-assembled structures decapeptide...
Disorder in proteins is vital for biological function, yet it challenging to characterize. Therefore, methods predicting protein disorder from sequence are fundamental. Currently, predictors trained and evaluated using data X-ray structures or various biochemical spectroscopic data. However, the prediction accuracy of disordered not calibrated, nor established whether intrinsically biased towards one extremes order-disorder axis. We therefore generated validated a comprehensive experimental...
Abstract Structural disorder is widespread in eukaryotic proteins and vital for their function diverse biological processes. It therefore highly desirable to be able predict the degree of order from amino acid sequence. is, however, notoriously difficult local flexibility within structured domains presence nuances localized rigidity intrinsically disordered regions. To identify such instances, we used CheZOD database, which encompasses accurate, balanced, continuous-valued quantification...
Two G-quadruplex forming sequences, 5′-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of ( R )-1- O -(pyren-1-ylmethyl)glycerol (intercalating acid, INA) -[4-(1-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating TINA). Incorporation LNA INA/TINA monomers provide as much 8-fold improvement activity. We demonstrate for first time a detailed analysis effect incorporation in...
Abstract Photosynthetic antenna systems enable organisms harvesting light and transfer the energy to photosynthetic reaction centre, where conversion chemical takes place. One of most complex systems, chlorosome, found in green sulfur bacterium Chlorobaculum (Cba.) tepidum contains a baseplate, which is scaffolding super-structure, formed by protein CsmA bacteriochlorophyll . Here we present first high-resolution structure baseplate using intact fully functional, light-harvesting organelles...
Abstract Die Fibrillenstruktur , die das amyloidogene Fragment SNNFGAILSS des menschlichen Insel‐Amyloid‐Polypeptids (hIAPP) bildet, wurde mit einer Auflösung von 0.52 Å bestimmt. Aus den Festkörper‐NMR‐Spektren einfach erhältliche Symmetrieinformationen (siehe Bild) können zusammen langreichweitigen Randbedingungen genutzt werden, um supramolekulare Organisation Fibrillen eindeutig zu identifizieren. magnified image
The JAK/STAT signaling pathway is suggested to play an important role in the pathogenesis of psoriasis, and recently inhibitors have shown promising results psoriasis treatment. present study aimed characterize STAT2 psoriasis. We demonstrated increased expression level phosphorylated/activated lesional compared with nonlesional psoriatic skin. Gene silencing by siRNA human keratinocytes revealed that upon IFNα stimulation CXCL11 CCL5 were only two cytokines, among 102 analyzed, found be...
During recent years, inborn errors of human IL-17 immunity have been demonstrated to underlie primary immunodeficiencies with chronic mucocutaneous candidiasis (CMC). Various defects in receptors responsible for sensing Candida albicans or downstream signalling may lead susceptibility infection. While CMC is common patients profound T cell immunodeficiencies, also recognised as part other syndromic CMC, relatively isolated disease. We describe a 40-year-old woman clinical picture involving...
The protein universe consists of a continuum structures ranging from full order to complete disorder. As the structured part proteome has been intensively studied, stably folded proteins are increasingly well documented and understood. However, that fully, or in large part, disordered much less characterized. Here we collected NMR chemical shifts small database for 117 sequences known contain We demonstrate shift data can be brought bear as an exquisite judge disorder at residue level, help...
Sharp curves: The structure of a locked nucleic acid modified telomeric sequence from Oxytricha nova displays remarkable folding topology, distinct the native O. quadruplex. Each guanine stretch folds back in V-shaped turn that puts first and fourth guanines same tetrad, looping over tetrad with sharp DNA backbone, showing how subtle interplay between conformation defines topology.
Alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) is a nucleotide analogue that raises the thermostability of acid duplexes by up to approximately 4 degrees C per inclusion. We have determined NMR structure nonamer alpha-L-LNA:RNA hybrid with three alpha-L-LNA modifications. The geometry this intermediate between A- and B-type, all nucleobases partake in Watson-Crick base pairing stacking, global very similar corresponding unmodified hybrid. sugar-phosphate backbone rearranged...
We have determined the NMR solution structures of quadruplexes formed by d(TGLGLT) and d(TL4T), where L denotes LNA (locked nucleic acid) modified G-residues. Both are tetrameric, parallel right-handed native global fold corresponding DNA quadruplex is retained upon introduction nucleotides. However, local structural alterations observed owing to locked sugars. In particular, a distinct change in sugar-phosphate backbone at G2pL3 L2pL3 base steps sequence dependent changes twist between...
Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and type of exosite interactions for phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), the serine murine urokinase-type plasminogen activator (uPA). We used X-ray crystal structure analysis, site-directed mutagenesis, liquid state NMR, surface plasmon resonance isothermal titration calorimetry wild engineered variants human uPA. that Arg6...
Dotting the i: The i-motif is a four-stranded DNA structure that consists of intercalated hemiprotonated C:C+ base pairs. Although they contain 2′-ribo oxygen atoms, LNA-modified TC5 oligonucleotides are also able to form stable tetrameric structures at low pH values (see view into one two narrow grooves such structure), as shown by combination CD, UV, and NMR spectroscopy. Supporting information for this article available on WWW under...
Many severe diseases are associated with amyloid fibril deposits in the body caused by protein misfolding. Structural information on fibrils is accumulating rapidly, but little known about assembly of peptides into at level individual molecules. Here we investigate self-assembly fibril-forming tetrapeptides KFFE and KVVE a gold surface under ultraclean vacuum conditions using scanning tunneling microscopy. Combined restrained molecular dynamics modeling, identify peptide arrangements...
A clever combination: an in situ solid-state NMR analysis of CsmA proteins the heterogeneous environment photoreceptor Chlorobaculum tepidum is reported. Using different combinations 2D and 3D spectra, 90 % resonances are assigned provide on basis chemical shift data information about structure conformation CsmA-bacteriochlorophyll a complex.
Abstract The development of protease inhibitors for pharmacological intervention has taken a new turn with the use peptide‐based inhibitors. Here, we report rational design bicyclic peptide serine urokinase‐type plasminogen activator (uPA), based on established monocyclic peptide, upain‐2. It was successfully converted to without loss inhibitory properties. aim produce cyclised by an amide bond additional stabilising across‐the‐ring covalent bond. We expected this exhibit lower entropic...