http://hdl.handle.net/10033/6840 Abt. Medizinische Chemie (MCH) Sun, 19 May 2013 12:33:28 GMT 2013-05-19T12:33:28Z http://hdl.handle.net/10033/283600 Title: The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89. Authors: Borst, Eva Maria; Kleine-Albers, Jennifer; Gabaev, Ildar; Babic, Marina; Wagner, Karen; Binz, Anne; Degenhardt, Inga; Kalesse, Markus; Jonjic, Stipan; Bauerfeind, Rudolf; Messerle, Martin Abstract: Cleavage of human cytomegalovirus (HCMV) genomes as well as their packaging into capsids is an enzymatic process mediated by viral proteins and therefore a promising target for antiviral therapy. The HCMV proteins pUL56 and pUL89 form the terminase and play a central role in cleavage-packaging, but several additional viral proteins, including pUL51, had been suggested to contribute to this process, although they remain largely uncharacterized. To study the function of pUL51 in infected cells, we constructed HCMV mutants encoding epitope-tagged versions of pUL51 and used a conditionally replicating virus (HCMV-UL51-ddFKBP), in which pUL51 levels could be regulated by a synthetic ligand. In cells infected with HCMV-UL51-ddFKBP, viral DNA replication was not affected when pUL51 was knocked down. However, no unit-length genomes and no DNA-filled C capsids were found, indicating that cleavage of concatemeric HCMV DNA and genome packaging into capsids did not occur in the absence of pUL51. pUL51 was expressed mainly with late kinetics and was targeted to nuclear replication compartments, where it colocalized with pUL56 and pUL89. Upon pUL51 knockdown, pUL56 and pUL89 were no longer detectable in replication compartments, suggesting that pUL51 is needed for their correct subnuclear localization. Moreover, pUL51 was found in a complex with the terminase subunits pUL56 and pUL89. Our data provide evidence that pUL51 is crucial for HCMV genome cleavage-packaging and may represent a third component of the viral terminase complex. Interference with the interactions between the terminase subunits by antiviral drugs could be a strategy to disrupt the HCMV replication cycle. Fri, 01 Feb 2013 00:00:00 GMT http://hdl.handle.net/10033/283600 2013-02-01T00:00:00Z http://hdl.handle.net/10033/265912 Title: Hypoxylon pulicicidum sp. nov. (Ascomycota, Xylariales), a pantropical insecticide-producing endophyte. Authors: Bills, Gerald F; González-Menéndez, Victor; Martín, Jesús; Platas, Gonzalo; Fournier, Jacques; Peršoh, Derek; Stadler, Marc Abstract: Nodulisporic acids (NAs) are indole diterpene fungal metabolites exhibiting potent systemic efficacy against blood-feeding arthropods, e.g., bedbugs, fleas and ticks, via binding to arthropod specific glutamate-gated chloride channels. Intensive medicinal chemistry efforts employing a nodulisporic acid A template have led to the development of N-tert-butyl nodulisporamide as a product candidate for a once monthly treatment of fleas and ticks on companion animals. The source of the NAs is a monophyletic lineage of asexual endophytic fungal strains that is widely distributed in the tropics, tentatively identified as a Nodulisporium species and hypothesized to be the asexual state of a Hypoxylon species. Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/10033/265912 2012-01-01T00:00:00Z http://hdl.handle.net/10033/246442 Title: Opening and closing of the bacterial RNA polymerase clamp. Authors: Chakraborty, Anirban; Wang, Dongye; Ebright, Yon W; Korlann, You; Kortkhonjia, Ekaterine; Kim, Taiho; Chowdhury, Saikat; Wigneshweraraj, Sivaramesh; Irschik, Herbert; Jansen, Rolf; Nixon, B Tracy; Knight, Jennifer; Weiss, Shimon; Ebright, Richard H Abstract: Using single-molecule fluorescence resonance energy transfer, we have defined bacterial RNA polymerase (RNAP) clamp conformation at each step in transcription initiation and elongation. We find that the clamp predominantly is open in free RNAP and early intermediates in transcription initiation but closes upon formation of a catalytically competent transcription initiation complex and remains closed during initial transcription and transcription elongation. We show that four RNAP inhibitors interfere with clamp opening. We propose that clamp opening allows DNA to be loaded into and unwound in the RNAP active-center cleft, that DNA loading and unwinding trigger clamp closure, and that clamp closure accounts for the high stability of initiation complexes and the high stability and processivity of elongation complexes. Fri, 03 Aug 2012 00:00:00 GMT http://hdl.handle.net/10033/246442 2012-08-03T00:00:00Z http://hdl.handle.net/10033/245811 Title: Design, synthesis and biological evaluation of simplified side chains of the macrolide antibiotic etnangien. Authors: Altendorfer, Mario; Irschik, Herbert; Menche, Dirk Abstract: Novel simplified side chains of the potent RNA polymerase inhibitor etnangien were designed, synthesized and evaluated for antibacterial activity against Gram-positive bacteria and one Gram-negative bacterium. Sat, 01 Sep 2012 00:00:00 GMT http://hdl.handle.net/10033/245811 2012-09-01T00:00:00Z