- Journal article
Authors : Courchaine, Edward M.; Barentine, Andrew E.S.; Straube, Korinna (2020) - At least one region of SMN employs a unifying mechanism of condensation. Unexpectedly, we show here that SMN’s globular tudor domain was sufficient for dimerization-induced condensation in vivo, while its two intrinsically disordered regions (IDRs) were not. The condensate-forming property of the SMN tudor domain required binding to its ligand, dimethylarginine (DMA), and was shared by at least seven additional tudor domains in six different proteins. Remarka...
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- Journal article
Authors : Andersen, Susan; Møller, Marie S; Poulsen, Jens-Christian N (2020) - The maltooligosaccharide (MOS) utilization locus in The degradation of starch in the small intestine generates short linear and branched α-glucans. The latter are poorly digestible by humans, rendering them available to the gut microbiota e.g. lactobacilli adapted to the human small intestine and considered as beneficial to health. This study unveils a previously unknown scheme of maltooligosaccharide (MOS) catabolism, via the concerted action of activity together...
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- Journal article
Authors : Beyer, Hannes M; Virtanen, Salla I; Aranko, A. Sesilja (2020) - The widely used molecular evolutionary clock assumes the divergent evolution of proteins. Convergent evolution has been proposed only for small protein elements but not for an entire protein fold. We investigated the structural basis of the protein splicing mechanism by class 3 inteins, which is distinct from class 1 and 2 inteins. We gathered structural and mechanistic evidence supporting the notion that the Hedgehog/INTein (HINT) superfamily fold, ...
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- Journal article
Authors : Patterson, Jenelle A; He, Hai; Folz, Jacob S (2020) - Formaldehyde (HCHO) is a reactive carbonyl compound that formylates and cross-links proteins, DNA, and small molecules. It is of specific concern as a toxic intermediate in the design of engineered pathways involving methanol oxidation or formate reduction. The high interest in engineering these pathways is not, however, matched by engineering-relevant information on precisely why HCHO is toxic or on what damage-control mechanisms cells deploy to manage HCHO&...
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- Journal article
Authors : Chang, Deborah; Hackett, William E; Zhong, Lei (2020) - Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity...
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- Journal article
Authors : Roopnarine, Osha; Thomas, David D. (2020) - the effects of ten actin binding compounds on the interaction of cardiac myosin subfragment 1 (S1) with pyrene labeled F actin (PFA). These compounds, previously identified from a small-molecule high-throughput screen (HTS), perturb the microsecond structural dynamics of actin and the steady-state activity of actin-activated myosin ATPase. In the present study, we have further characterized their mechanisms of action by measuring their effects on PFA fluorescence,...
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Authors : Sarkar, Snigdha; Gu, Wenjia; Schmidt, Eric W (2020) - Cyclic peptides are excellent drug candidates, placing macrocyclization reactions at the apex of drug development. PatG and related dual-action proteases from cyanobactin biosynthesis are responsible for cleaving off the C-terminal recognition sequence and macrocyclizing the substrate to provide cyclic peptides. This reaction has found use in the enzymatic synthesis of diverse macrocycles. However, these enzymes function best on substrates that terminate with the non-protei...
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- Journal article
Authors : Vogel, Dominik; Thorkelsson, Sigurdur Rafn; Quemin, Emmanuelle R. J (2020) - The Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever with thrombocytopenia syndrome virus (SFTSV). The lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment of any virus outbreak. To develop such antivirals a profound understanding of the viral replication process is essential. The L protein of bunyaviruses is a multi-functional and multi-domain protein pe...
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- Journal article
Authors : Sorrell, Fiona J; Miranda, Fabrizio; Azeez, Kamal R. Abdul (2020) - The STK32 kinases are a small subfamily of three uncharacterised serine/threonine kinases from the AGC kinase family whose functional role is so far unknown. Here, we analyse the consensus peptide sequence for STK32A phosphorylation, showing that STK32A is directed towards acidic substrate sequences and exhibits dual-specificity for serine/threonine and tyrosine residues. A crystal structure of STK32A reveals an overall structure typical of the AGC protein&#x...
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- Journal article
Authors : Mäeots, Märt-Erik; Lee, Byungjin; Nans, Andrea (2020) - Mechanistic understanding of biochemical reactions requires structural and kinetic characterization of the underlying chemical processes. However, no single experimental technique can provide this information in a broadly applicable manner and thus structural studies of static macromolecules are often complemented by biophysical analysis. Moreover, the common strategy of utilizing mutants or crosslinking probes to stabilize otherwise short-lived reaction intermediates is prone to tra...
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