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  • Journal article

  • Development of fluorescence polarization-based competition assay for nicotinamide N-methyltransferase

    • Authors : Iyamu, Iredia D; Huang, Rong (2020)

  • Methylation-mediated pathways play an important role in the progression of cancer. Inhibitors of several key methyltransferases including DNA methyltransferases and histone methyltransferases have proven to be instrumental for both understanding the function of the respective enzymes activites and translational applications in cancer epigenetic therapy. Nicotinamide N-methyltransferase (NNMT) is a major metabolic enzyme involved in epigenetic regulation through catalysis of methyl transfe...
  • Journal article

  • Membrane Insertion of Mycobacterium tuberculosis EsxA in Cultured Lung Epithelial Cells

    • Authors : Zhang, Qi; Aguilera, Javier; Reyes, Salvador Vazquez (2020)

  • EsxA has long been recognized as an important virulence factor of Mycobacterium tuberculosis (Mtb) that plays an essential role in Mtb virulence. However, current data regarding to its role in Mtb virulence are controversial. Here, we have obtained evidence showing that the cytolytic activity of EsxA at neutral pH is due to contamination of ASB-14, a detergent used in EsxA preparation. Moreover, it is for the first time we have found ...
  • Journal article

  • Peripheral blood mononuclear cells preferentially activate 11-oxygenated androgens

    • Authors : - (2020)

  • PBMCs generated 8-fold higher amounts of the active 11-oxygenated androgen 11- ketotestosterone than the classic androgen testosterone from their respective precursors. We identified the enzyme AKR1C3 as the major reductive 17β-hydroxysteroid dehydrogenase in PBMCs responsible for both conversions and found that within the PBMC compartment natural killer cells are the major site of AKRC13 expression and activity. Steroid 5α-reductase type 1 c...
  • Journal article

  • Fine interaction profiling of VemP and mechanisms responsible for its translocation-coupled arrest-cancelation

    • Authors : Miyazaki, Ryoji; Akiyama, Yoshinori; Mori, Hiroyuki (2020)

  • To attempt at delineating the pathway of the VemP nascent-chain interaction with Sec-related factors, and identified the signal recognition particle (SRP) and PpiD (a membrane-anchored periplasmic chaperone) in addition to other translocon components and a ribosomal protein as interacting partners. Our results showed that SRP is required for the membrane-targeting of VemP, whereas PpiD acts cooperatively with SecD/F in the VemP arrest-cancelation. We also identifi...
  • Journal article

  • Tyrosine phosphorylation regulates hnRNPA2 granule protein partitioning & reduces neurodegeneration

    • Authors : Ryan, Veronica H; Perdikari, Theodora Myrto; Naik, Mandar T (2020)

  • mRNA transport in neurons is a ubiquitous process but has been often overlooked as a contributor to disease. Mutations of transport granule protein hnRNPA2 cause hereditary proteinopathy of neurons, myocytes, and bone. Here, we examine transport granule component specificity, assembly/disassembly, and the link to neurodegeneration. hnRNPA2 transport granule components hnRNPF and ch-TOG interact weakly with hnRNPA2 yet they each partition specifically into hnRNPA2 liqui...
  • Journal article

  • Semi-processive hyperglycosylation of adhesin by bacterial protein N-glycosyltransferases

    • Authors : Yakovlieva, Liubov; Ramírez-Palacios, Carlos; Marrink, Siewert J. (2020)

  • Processivity is an important feature of enzyme families such as DNA polymerases, polysaccharide synthases and protein kinases, to ensure high fidelity in biopolymer synthesis and modification; reveal processive character in the family of cytoplasmic protein N-glycosyltransferases (NGTs). Through various activity assays, intact protein mass spectrometry and proteomics analysis, we established that NGTs from non-typeable Haemophilus influenzae and Actinobacillus pleuropneumoniae modify an&#...
  • Journal article

  • CO2 reduction driven by a pH gradient

    • Authors : Hudson, Reuben; Graaf, Ruvan de; Rodin, Mari Strandoo (2020)

  • All life on Earth is built of organic molecules, so the primordial sources of reduced carbon are a major open question in studies of the origin of life. A variant of the alkaline-vent theory suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog—and proposed evolutionary predecessor—of the modern Wood-Ljungdahl acetyl-Co-A&#x...
  • Journal article

  • Structural basis for binding mechanism of human serum albumin complexed with cyclic peptide dalbavancin

    • Authors : Yakovlieva, Liubov; Ramírez-Palacios, Carlos; Marrink, Siewert J. (2020)

  • Cyclic peptides, with unique structural features, have emerged as new candidates for drug discovery; their association with human serum albumin (HSA; long blood half-life), is crucial to improve drug delivery and avoid renal clearance. Here, we present the crystal structure of HSA complexed with dalbavancin, a clinically used cyclic peptide. SAXS and ITC experiments showed that the HSA-dalbavancin complex exists in a monomeric state; dalbavancin is only ...