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Showing results 1 to 19 of 19
  • OER000002427.pdf.jpg
  • Ebooks (Sách điện tử)

  • A TREX1 model reveals double-strand DNA preference and inter-protomer regulation

    • Authors : Hemphill, Wayne O. (2023)

  • The TREX1 3’ à 5’ exonuclease degrades DNA in vivo to prevent chronic immune activation through the cGAS-STING pathway. TREX1 degrades ss- and dsDNA containing a free 3’-hydroxyl, but the precise nature of immune-activating DNA remains an open question. The TREX1 homodimer structure is critical for exonuclease activity with amino acids from one protomer acting across the dimer interface contributing to catalysis in the opposing protomer.&#x...
  • OER000002748.pdf.jpg
  • Journal article

  • Computationally Guided Design of Novel Angiotensin Converting Enzyme Inhibitors

    • Authors : Lam, Jennifer D. (2023)

  • Angiotensin-converting enzyme inhibitors (ACEI) such as Moexipril, Trandolapril, Ramipril, and Perindopril are used to treat hypertension. However, these drugs have undesired side effects. Using computational studies, two new novel drug candidates were designed with improved molecular interactions, ADMET properties, and docking scores compared to Moexipril. Homology analysis was done to determine the best animal model for preclinical studies, and it revealed that Pan troglo...
  • OER000002325.pdf.jpg
  • Journal Article

  • Contribution of amino acids in the Active site of Dipeptidyl Peptidase 4 to the catalytic action of the enzyme

    • Authors : Gnoth, Kathrin (2023)

  • Dipeptidyl peptidase 4 (DP4)/CD26 regulates the biological function of various peptide hormones by releasing dipeptides from their N-terminus. The enzyme is a prominent target for the treatment of type-2 diabetes and various DP4 inhibitors have been developed in recent years, but their efficacy and side effects are still an issue. Many available crystal structures of the enzyme give a static picture about enzyme-ligand interactions,&...
  • OER000002681.pdf.jpg
  • Journal article

  • Designed high-redox potential laccases exhibit high functional diversity

    • Authors : Zucker, Shiran Barber (2023)

  • White-rot fungi secrete an impressive repertoire of high-redox potential laccases (HRPLs) and peroxidases for efficient oxidation and utilization of lignin. Laccases are attractive enzymes for greenchemistry applications due to their broad substrate range and low environmental impact. Since expression of functional recombinant HRPLs is challenging, however, iterative directed evolution protocols have been applied to improve their expression, activity and stability. ...
  • OER000002599.pdf.jpg
  • Journal article

  • Discovery and characterization of non-canonical E2 conjugating enzymes

    • Authors : Rehman, Syed Arif Abdul  (2023)

  • E2 conjugating enzymes (E2s) play a central role in the enzymatic cascade that leads to the 20 attachment of ubiquitin to a substrate. This process, termed ubiquitylation is fundamental for 21 maintaining cellular homeostasis and impacts almost all cellular process. By interacting with 22 multiple E3 ligases, E2s direct the ubiquitylation landscape within the cell. Since its discovery, 23 ubiquitylation has been regarded as a post-translational modification&#...
  • OER000002280.pdf.jpg
  • Journal Article

  • Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase

    • Authors : Linnea Klara Maryann Blomgren (2023)

  • One-carbon metabolism drives an extensive network of signalling and biosynthetic pathways 17 essential for cell growth and redox regulation. In all domains of life, 5,10-18 methylenetetrahydrofolate reductase (MTHFR) signals the commitment of folate-derived one-19 carbon units into biosynthesis of the global donor of trans-methylation, S-adenosyl-L-methionine 20 (SAM). Eukaryotic MTHFR appends to its conserved TIM-barrel catalytic domain (CD) a unique 21 regulatory domain (RD)&#...
  • OER000002573.pdf.jpg
  • Journal article

  • Enzymatic assay for UDP-GlcNAc and its application in the parallel assessment of substrate availability and protein O-GlcNAcylation

    • Authors : Sunden, Marc (2023)

  • O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous and dynamic yet still relatively poorly understood non-canonical glycosylation of intracellular proteins. Several vital branches of metabolism converge at the hexosamine biosynthetic pathway (HBP) to produce the substrate for protein O-GlcNAcylation the uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Availability of this metabolite is considered a key regulator of O-GlcNAcylation. Yet UDP-GlcNAc concentrations ...
  • OER000002360.pdf.jpg
  • Journal Article

  • FruitFire: a luciferase based on a fruit fly metabolic enzyme

    • Authors : Adams Jr., Spencer T. (2023)

  • Firefly luciferase is homologous to fatty acyl-CoA synthetases from insects that are not bioluminescent. Here, we determined the crystal structure of the fruit fly fatty acyl-CoA synthetase CG6178 to 2.5 Å. Based on this structure, we mutated a steric protrusion in the active site to create the artificial luciferase FruitFire, which prefers the synthetic luciferin CycLuc2 to D-luciferin by >1000-fold. FruitFire enabled in vivo bioluminescence...
  • OER000002503.pdf.jpg
  • Journal article

  • Identification of a new Corin atrial natriuretic peptide-converting enzyme substrate: Agouti-signaling protein (ASIP)

    • Authors : MacDonald, Bryan T.  (2023)

  • Corin is a transmembrane tethered enzyme best known for processing the hormone atrial natriuretic peptide (ANP) in cardiomyocytes to control electrolyte balance and blood pressure. Loss of function mutations in Corin prevent ANP processing and lead to hypertension. Curiously, Corin loss of function variants also result in lighter coat color pigmentation in multiple species. Corin pigmentation effects are dependent on a functional Agouti locus encoding the ago...
  • OER000002955.pdf.jpg
  • Journal article

  • Metabolic response to point mutations reveals principles of modulation of in vivo enzyme activity and phenotype

    • Authors : Bhattacharyya, Sanchari (2021)

  • The relationship between sequence variation and phenotype is poorly understood. Here we use metabolomic analysis to elucidate the molecular mechanism underlying the filamentous phenotype of E. coli strains that carry destabilizing mutations in Dihydrofolate Reductase (DHFR). We find that partial loss of DHFR activity causes reversible filamentation despite SOS response indicative of DNA damage, in contrast to thymineless death (TLD) achieved by complete inhibition of&#...
  • OER000002544.pdf.jpg
  • Journal article

  • Novel glycoside hydrolase family enzymes from Escherichia coli are associated with osmo-regulated periplasmic glucan synthesis

    • Authors : Motouchi, Sei (2023)

  • Most Gram-negative bacteria synthesize osmo-regulated periplasmic glucans (OPG) in the periplasm or extracellular space. Many pathogens lose their pathogenicity by knocking out opgG, an OPG-related gene indispensable for OPG synthesis. However, the biochemical functions of OpgG and OpgD, a paralog of OpgG, have not been elucidated. In this report, structural and functional analyses of OpgG and OpgD from Escherichia coli revealed that these proteins are β-1,2-gluca...
  • OER000002371.pdf.jpg
  • Journal Article

  • Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase

    • Authors : Díaz, Roberto Efraín (2023)

  • Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, w...
  • OER000002614.pdf.jpg
  • Journal article

  • The cardiac myosin binding protein-C phosphorylation state as a function of multiple protein kinase and phosphatase activities

    • Authors : Kampourakis, Thomas (2023)

  • Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) is a crucial determinant of cardiac myofilament function. Although cMyBP-C phosphorylation by various protein kinases has been extensively studied, the influence of protein phosphatases on cMyBP-C’s multiple phosphorylation sites has remained largely obscure. Here we provide a detailed biochemical characterization of cMyBP-C dephosphorylation by protein phosphatases 1 and 2A (PP1 and PP2A) and deve...