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  • Journal article

  • Glycoproteomic measurement of site-specific polysialylation

    • Authors : Pelingon, Ruby; Pegg, Cassandra L; Zacchi, Lucia F (2020)

  • Polysialylation is the enzymatic addition of a highly negatively charged sialic acid polymer to the non-reducing termini of glycans. Polysialylation plays an important role in development, and is involved in neurological diseases, neural tissue regeneration, and cancer. Polysialic acid (PSA) is also a biodegradable and non-immunogenic conjugate to therapeutic drugs to improve their pharmacokinetics. PSA chains vary in length, composition, and linkages, while the specif...
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  • Application of petri nets methodoloydy for the examination of the bio(physico)chemical parameters of mitochodria funtioning

    • Authors : Danylovych, Hanna V; Chunikhin, Alexander Yu; Danylovych, Yuriy V (2020)

  • A mathematical model is developed using Petri net methodology that is able to predict simultaneous changes in bio(physical)chemical parameters of mitochondria, namely hydrodynamic diameter, fluorescence of NADH, DCF fluorescence signal depending on the time of action and concentration of sodium azide and predict these changes for unknown NaN3 concentration. The model is created for real experimental conditions, it combines functional changes of mitochondria with a ...
  • Journal article

  • Production and Purification of Endogenously Modified tRNA-Derived Small RNAs

    • Authors : Drino, Aleksej; Oberbauer, Vera; Troger, Conor (2020)

  • During particular stress conditions, transfer RNAs (tRNAs) become substrates of stress-induced endonucleases, resulting in the production of distinct tRNA-derived small RNAs (tsRNAs). These small RNAs have been implicated in a wide range of biological processes, but how isoacceptor and even isodecoder-specific tsRNAs act at the molecular level is still poorly understood. Importantly, stress-induced tRNA cleavage affects only a few tRNAs of a given isoacceptor or i...
  • Journal article

  • System-wide identification and prioritization of enzyme substrates by thermal analysis (SIESTA)

    • Authors : Saei, Amir Ata; Beusch, Christian M; Sabatier, Pierre; Wells, Juan Astorga (2020)

  • Despite the immense importance of enzyme-substrate reactions, there is a lack of generic and unbiased tools for identifying and prioritizing substrate proteins which are modulated in the structural and functional levels through modification. Here we describe a high-throughput unbiased proteomic method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that enzymatic post-translational modification of substrate&...
  • Journal article

  • A novel G protein-biased and subtype selective agonist for a G protein-coupled receptor discovered from screening herbal extracts

    • Authors : Zhang, Bingjie; Zhao, Simeng; Yang, Dehua (2020)

  • Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal&#...
  • Industry article

  • Ribosome association primes the stringent factor Rel for recruitment of deacylated tRNA to ribosomal A-site

    • Authors : Takada, Hiraku; Roghanian, Mohammad; Montes, Julien Caballero (2020)

  • In the Gram-positive Firmicute bacterium Bacillus subtilis, amino acid starvation induces synthesis of the alarmone (p)ppGpp by the multi-domain RelA/SpoT Homolog factor Rel. This bifunctional enzyme is capable of both synthesizing and hydrolysing (p)ppGpp. To detect amino acid deficiency, Rel monitors the aminoacylation status of the ribosomal A-site tRNA by directly inspecting the tRNA’s CCA end. Here we uncover the molecular mechanism of Rel-mediated stringent&...
  • Journal article

  • Succinate can shuttle reducing power from the hypoxic retina to the O2-rich pigment epithelium

    • Authors : Bisbach, Celia M; Hass, Daniel T; Robbings, Brian M (2020)

  • When O2 is plentiful, the mitochondrial electron transport chain uses it as a terminal electron acceptor. However, the mammalian retina thrives within a hypoxic niche in the eye. We find that mitochondria in retinas adapt to their hypoxic environment by relying on the “reverse” succinate dehydrogenase reaction, where fumarate accepts electrons instead of O2. Reverse succinate dehydrogenase activity produces succinate and is enhanced by down-regulation of cyto...