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Mechanism of Action of the Ribopyranoside Benzimidazole GW275175X against Human Cytomegalovirus. Mark R. Underwood, 2004.New human cytomegalovirus (HCMV) therapies with novel mechanisms of action are needed to treat drug-resistant HCMV that arises during therapy with currently approved agents . 2-Bromo-5,6-dichloro-1-ß-D-ribofuranosyl-1H-benzimidazole (BDCRB) is an effective anti-HCMV agent with a novel mechanism of action, but problems with in vivo stability preclude clinical development . A D-ribopyranosyl derivative of BDCRB, GW275175X, displays similar antiviral activity without the in vivo stability problems . We present an initial description of the activity of GW275175X against HCMV, other herpesviruses, and selected nonherpesviruses . In addition, we show that it acts as a DNA maturation inhibitor like the parent compound, BDCRB, rather than via the mechanisms of action of 1263W94 or any anti-HCMV drugs approved for marketing . GW275175X is a promising candidate for clinical development as an anti-HCMV agent . Spatiotemporal Distribution of Marine Magnetotactic Bacteria in a Seasonally Stratified Coastal Salt Pond. S. L. Simmons, 2004.The occurrence and distribution of magnetotactic bacteria (MB) were studied as a function of the physical and chemical conditions in meromictic Salt Pond, Falmouth, Mass., throughout summer 2002 . Three dominant MB morphotypes were observed to occur within the chemocline . Small microaerophilic magnetite-producing cocci were present at the top of the chemocline, while a greigite-producing packet-forming bacterium occurred at the base of the chemocline . The distributions of these groups displayed sharp changes in abundance over small length scales within the water column as well as strong seasonal fluctuations in population abundance . We identified a novel, greigite-producing rod in the sulfidic hypolimnion that was present in relatively constant abundance over the course of the season . This rod is the first MB that appears to belong to the  -Proteobacteria, which may suggest an iron- rather than sulfur-based respiratory metabolism . Its distribution and phylogenetic identity suggest that an alternative model for the ecological and physiological role of magnetotaxis is needed for greigite-producing MB .
Membrane Protein Degradation by FtsH Can Be Initiated from Either End. Shinobu Chiba, 2002.FtsH, a membrane-bound metalloprotease, with cytoplasmic metalloprotease and AAA ATPase domains, degrades both soluble and integral membrane proteins in Escherichia coli . In this paper we investigated how membrane-embedded substrates are recognized by this enzyme . We showed previously that FtsH can initiate processive proteolysis at an N-terminal cytosolic tail of a membrane protein, by recognizing its length (more than 20 amino acid residues) but not exact sequence . Subsequent proteolysis should involve dislocation of the substrates into the cytosol . We now show that this enzyme can also initiate proteolysis at a C-terminal cytosolic tail and that the initiation efficiency depends on the length of the tail . This mode of degradation also appeared to be processive, which can be aborted by a tightly folded periplasmic domain . These results indicate that FtsH can exhibit processivity against membrane-embedded substrates in either the N-to-C or C-to-N direction . Our results also suggest that some membrane proteins receive bidirectional degradation simultaneously . These results raise intriguing questions about the molecular directionality of the dislocation and proteolysis catalyzed by FtsH . Determination of the InvE Binding Site Required for Expression of IpaB of the Shigella sonnei Virulence Plasmid: Involvement of a ParB BoxA-Like Sequence. Takayuki Taniya, 2003.The InvE protein positively regulates the expression of virulence genes ipaBCD in Shigella sonnei . The InvE has significant homology with ParB of plasmid P1, which is known as a plasmid partitioning factor with DNA binding ability . Although the DNA binding activity of InvE has been predicted, it is not known whether the DNA binding activity is necessary for type III secretion system-associated gene expression . In this study, we determined the transcription start site of the icsB-ipaBCD operon (ipa operon) and constructed a series of deletions of the icsB promoter region in the Escherichia coli K-12 background . The deletion study revealed that an 86-bp region upstream of the icsB transcription start site was essential for expression of the ipa operon, where the ParB binding motif (ParB BoxA-like sequence) was observed . Purified glutathione S-transferase-InvE fusion protein bound directly to the -93 to -54 region (designating the icsB transcription start site as nucleotide +1) containing the ParB BoxA-like sequence . These results indicated that InvE bound directly to the promoter region .
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