Whole genome sequence of a freshwater agar-degrading bacterium Cellvibrio sp. KY-GH-1.

We investigated the whole genome sequence of a freshwater agar-degrading bacterium Cellvibrio sp. KY-GH-1 (KCTC13629BP) to explore genetic information encoding agarases which hydrolyze agar into its monomers. The complete genome of KY-GH-1 comprised 5,762,391 base pairs (bp) with 47.9% GC content, and contained 5080 protein-encoding sequences, including nine ß-agarase genes and two α-neoagarobiose hydrolase (α-NABH) genes in an agarase gene cluster spanning approximately 77 kb. Based on these genetic information, the degradation of agar into monomers (D-galactose and 3,6-anhydro-L-galactose) by KY-GH-1 was predicted to be initiated by endolytic GH16 ß-agarases and endolytic GH86 ß-agarases, further processed by exolytic GH50 ß-agarases, and then terminated by exolytic GH117 α-NABHs. This study reveals the diversity and abundance of agarase genes, and provides insight into their roles in the agar-degrading enzyme machinery of Cellvibrio sp. KY-GH-1.

Pro-Apoptotic Role of the Human YPEL5 Gene Identified by Functional Complementation of a Yeast moh1Δ Mutation.

To examine the pro-apoptotic role of the human ortholog (YPEL5) of the Drosophila Yippee protein, the cell viability of Saccharomyces cerevisiae mutant strain with deleted MOH1, the yeast ortholog, was compared with that of the wild-type (WT)-MOH1 strain after exposure to different apoptogenic stimulants, including UV irradiation, methyl methanesulfonate (MMS), camptothecin (CPT), heat shock, and hyperosmotic shock. The moh1Δ mutant exhibited enhanced cell viability compared with the WT-MOH1 strain when treated with lethal UV irradiation, 1.8 mM MMS, 100 µ CPT, heat shock at 50°C, or 1.2 M KCl. At the same time, the level of Moh1 protein was commonly up-regulated in the WT-MOH1 strain as was that of Ynk1 protein, which is known as a marker for DNA damage. Although the enhanced UV resistance of the moh1Δ mutant largely disappeared following transformation with the yeast MOH1 gene or one of the human YPEL1-YPEL5 genes, the transformant bearing pYES2-YPEL5 was more sensitive to lethal UV irradiation and its UV sensitivity was similar to that of the WT-MOH1 strain. Under these conditions, the UV irradiation-induced apoptotic events, such as FITC-Annexin V stainability, mitochondrial membrane potential (ΔΨm) loss, and metacaspase activation, occurred to a much lesser extent in the moh1Δ mutant compared with the WT-MOH1 strain and the mutant strain bearing pYES2-MOH1 or pYES2-YPEL5. These results demonstrate the functional conservation between yeast Moh1 and human YPEL5, and their involvement in mitochondria-dependent apoptosis induced by DNA damage.

Development of 3D-QSAR CoMSIA models for 5-(biphenyl-2-yl)-1H-tetrazole derivatives as angiotensin II receptor type 1 (AT1) antagonists.

As a development strategy for backups of Fimasartan (1), a comparative molecular similarity indices analysis (CoMSIA) of a set of sixty-five 5-(biphenyl-2-yl)-1H-tetrazole derivatives has been performed to find out the pharmacophore elements for angiotensin II receptor type 1 (AT1) blockade. The most potent compound containing pyrimidin-4(3H)-one ring, Fimasartan (1) was used to align the molecules. As a result, we obtained 3D-QSAR model which provided good predictivity for both the training set (q(2)=0.846, r(2)=0.975) and the external test set (rpred(2)=0.980). This model would guide the design of backups for Fimasartan (1), a launched oral antihypertensive agent.