scholarly journals Biodiversity of CS–proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis

2018 ◽  
Vol 475 (3) ◽  
pp. 587-620 ◽  
Author(s):  
Anthony Hayes ◽  
Kazuyuki Sugahara ◽  
Brooke Farrugia ◽  
John M. Whitelock ◽  
Bruce Caterson ◽  
...  
Keyword(s):  
Information Transfer ◽  
Enzyme Inhibitors ◽  
Chondroitin Sulphate ◽  
Chain Structure ◽  
Bioactive Molecules ◽  
Biological Information ◽  
Extracellular Milieu ◽  
Overwhelming Evidence ◽  
Chemical Messenger ◽  
Cellular Behaviour

Chondroitin sulphate (CS) glycosaminoglycan chains on cell and extracellular matrix proteoglycans (PGs) can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the CS chain structure are a source of significant biological information to cells and their surrounding environment. CS sulphation motifs have been shown to interact with a wide variety of bioactive molecules, e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways, thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Consequently, through these motifs, CS PGs play significant roles in the maintenance of tissue homeostasis, morphogenesis, development, growth and disease. Here, we review (i) the biodiversity of CS PGs and their sulphation motif sequences and (ii) the current understanding of the signalling roles they play in regulating cellular behaviour during tissue development, growth, disease and repair.

scholarly journals Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5078 ◽  
Author(s):  
Walter J. Lukiw ◽  
Aileen I. Pogue
Keyword(s):  
Information Transfer ◽  
Biological Information ◽  
Messenger Rnas ◽  
Innate Immune Signaling ◽  
Cells Of Origin ◽  
Metabolic Products ◽  
Inflammatory Phenotype ◽  
The Central Nervous System ◽  
Neuro Inflammation ◽  
End Stage

Exosomes (EXs) and extracellular microvesicles (EMVs) represent a diverse assortment of plasma membrane-derived nanovesicles, 30–1000 nm in diameter, released by all cell lineages of the central nervous system (CNS). They are examples of a very active and dynamic form of extracellular communication and the conveyance of biological information transfer essential to maintain homeostatic neurological functions and contain complex molecular cargoes representative of the cytoplasm of their cells of origin. These molecular cargoes include various mixtures of proteins, lipids, proteolipids, cytokines, chemokines, carbohydrates, microRNAs (miRNA) and messenger RNAs (mRNA) and other components, including end-stage neurotoxic and pathogenic metabolic products, such as amyloid beta (Aβ) peptides. Brain microglia, for example, respond to both acute CNS injuries and degenerative diseases with complex reactions via the induction of a pro-inflammatory phenotype, and secrete EXs and EMVs enriched in selective pathogenic microRNAs (miRNAs) such as miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155, and others that are known to promote neuro-inflammation, induce complement activation, disrupt innate–immune signaling and deregulate the expression of neuron-specific phosphoproteins involved in neurotropism and synaptic signaling. This communication will review our current understanding of the trafficking of miRNA-containing EXs and EMVs from astrocytes and “activated pro-inflammatory” microglia to target neurons in neurodegenerative diseases with an emphasis on Alzheimer’s disease wherever possible.

scholarly journals Sequential degradation of a chondroitin sulphate trisaccharide by lysosomal enzymes from embryonic-chick epiphysial cartilage

1979 ◽  
Vol 179 (1) ◽  
pp. 7-13 ◽  
Author(s):  
B Ingmar ◽  
A Wasteson
Keyword(s):  
Lysosomal Enzymes ◽  
Glucuronic Acid ◽  
Enzyme Inhibitors ◽  
Functional Unit ◽  
Chondroitin Sulphate ◽  
Cartilage Degradation ◽  
Ester Group ◽  
Embryonic Chick ◽  
Reaction Products ◽  
Epiphysial Cartilage

The disulphated trisaccharide D-N-acetylgalactosamine sulphate-beta-D-glucuronic acid-beta-D-N-acetylgalactosamine sulphate prepared from 35S- or 14C-labelled chondroitin sulphate was incubated with a preparation of lysosomal enzymes from embryonic-chick epiphysial cartilage. Degradation was demonstrated by analysis of the reaction products. By use of the appropriate intermediate products as substrates, in conjunction with specific enzyme inhibitors, it was shown that the degradation proceeded sequentially from the non-reducing end. It was initiated by sulphatase (preferentially hydrolysing sulphate ester groups at the 6-position), followed by beta-N-acetylgalactosaminidase and beta-glucuronidase, converting the substrate into monosaccharides and inorganic sulphate. The latter enzyme preferentially attacked disaccharides carrying their sulphate ester group at C-4 of the hexosamine residue. Generation of chondroitin sulphate oligosaccharides may occur by the action of an endoglycosidase, previously demonstrated in embryonic-chick cartilage. Endo- and exo-enzymes may thus form a functional unit in lysosomal degradation of chondroitin sulphate.

scholarly journals Natural Bioactive Molecules as Potential Agents Against SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Chen ◽  
Zhihao Wang ◽  
Yawen Wang ◽  
Yiping Li
Keyword(s):  
Life Cycle ◽  
Antiviral Drug ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Biological Information ◽  
Economic Damage ◽  
Host Proteins ◽  
The Past ◽  
Invasion Mechanisms ◽  
The World

In the past two decades, pandemics of several fatal coronaviruses have posed enormous challenges for public health, including SARS-CoV (2003), MERS-CoV (2012), and SARS-CoV-2 (2019). Among these, SARS-CoV-2 continues to ravage the world today and has lead to millions of deaths and incalculable economic damage. Till now, there is no clinically proven antiviral drug available for SARS-CoV-2. However, the bioactive molecules of natural origin, especially medicinal plants, have been proven to be potential resources in the treatment of SARS-CoV-2, acting at different stages of the viral life cycle and targeting different viral or host proteins, such as PLpro, 3CLpro, RdRp, helicase, spike, ACE2, and TMPRSS2. They provide a viable strategy to develop therapeutic agents. This review presents fundamental biological information on SARS-CoV-2, including the viral biological characteristics and invasion mechanisms. It also summarizes the reported natural bioactive molecules with anti-coronavirus properties, arranged by their different targets in the life cycle of viral infection of human cells, and discusses the prospects of these bioactive molecules for the treatment of COVID-19.

scholarly journals Insuperable problems of the genetic code initially emerging in an RNA World

2017 ◽  
Author(s):  
Peter R Wills ◽  
Charles W Carter
Keyword(s):  
Protein Synthesis ◽  
Information Processing ◽  
Natural Selection ◽  
Information Transfer ◽  
Rna World ◽  
Biological Information ◽  
Universal System ◽  
Biological Information Processing ◽  
Relationship Of ◽  
The Relationship

AbstractDifferential equations for error-prone information transfer (template replication, transcription or translation) are developed in order to consider, within the theory of autocatalysis, the advent of coded protein synthesis. Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide•RNA world.

Binding Mode Prediction and Identification of New Lead Compounds from Natural Products as 3-OST Enzyme Inhibitors

2020 ◽  
Vol 17 (9) ◽  
pp. 1186-1196
Author(s):  
Rui Sousa ◽  
Narayana Subbiah Hari Narayana Moorthy ◽  
Pedro Alexandrino Fernandes ◽  
Maria Joao Ramos ◽  
Natércia Fernandes Brás
Keyword(s):  
Model Building ◽  
Enzyme Inhibitors ◽  
Pharmacophore Model ◽  
Binding Mode ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Mode Analysis ◽  
Viral Diseases ◽  
Interaction Sites ◽  
Screening Study

Background and Introduction: The availability of antiviral medicines for the treatment of viral diseases is limited, hence the discovery of novel bioactive molecules is required. The present investigation has been carried out to develop novel 3-O-sulfotransferase enzyme inhibitors to treat viral diseases. Method: Virtual screening study (QSAR, docking and pharmacophore analysis) and binding mode analysis have been performed on a dataset collected from the literature (synthetic and natural compounds). Results: The docking studies showed that Glu184, His186, Lys215 and Lys368 residues established the most important hydrogen bonding with several hit compounds. The QSAR results explained that the presence of electronegative atoms/groups in the aromatic or heteroaromatic rings confer increased activity. Furthermore, the flexibility and the aromatic rings with less polar groups have better activity than the compounds connected to purine rings. Finally, the structurebased pharmacophore studies illustrated that the ligand has many polar interaction sites, and the projected acceptor and donor groups in the molecules make a significant contribution to the pharmacophore model building. Conclusion: These studies identified two compounds, Phomoidride B and Barceloneic acid A, as potential 3-OST inhibitors.

scholarly journals Nuclear magnetic resonance studies of ribonucleic acids

2003 ◽  
Vol 17 (2-3) ◽  
pp. 537-547 ◽  
Author(s):  
Oliver Ohlenschläger ◽  
Jens Wöhnert ◽  
Ramadurai Ramachandran ◽  
Christian Sich ◽  
Matthias Görlach
Keyword(s):  
Information Transfer ◽  
Residual Dipolar Couplings ◽  
Protein Complexes ◽  
Pulse Sequences ◽  
Biological Information ◽  
Base Pairs ◽  
Stable Isotope Labelling ◽  
Ribonucleic Acids ◽  
Hydrogen Bonding Pattern ◽  
Essential Components

Ribonucleic acids (RNA) and RNA−protein complexes are essential components of biological information transfer, catalytic processes and are associated with regulatory functions. This broad range of biological functions is paralleled at the conformational level by a large number of non-canonical structural elements or sequences with non-standard backbone conformations, e.g., loops, bulges, pseudo-knots and complex tertiary folds. NMR spectroscopy has evolved to a powerful tool for the determination of ribonucleic acid structures of up to 20 kDa. Uniform or selective stable isotope labelling aids in solving assignment problems arising from the inherently limited chemical shift dispersion and overlap of resonances for larger nucleotide sequences. Recent developments of multi-dimensional heteronuclear NMR pulse sequences allow e.g., to directly observe the hydrogen bonding pattern of canonical Watson−Crick base pairs as well as of unusual types of base pairs, thereby opening up a fast access to secondary structure screening of RNA. Detailed conformational descriptions are obtained using conventional NOE andJcoupling-derived data, nowadays supplemented by information from residual dipolar couplings. The latter method also provides a new means for the probing of dynamical features of ribonucleic acids.

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