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81.
Echotoxins are hemolytic and lethal proteinaceous toxins of about 25 kDa that are contained in the salivary gland of marine
gastropod Monoplex echo. In this study, complementary DNAs (cDNAs) encoding four echotoxins (2, A, B1 and B2) were isolated from the cDNA library
constructed from the M. echo salivary gland and completely sequenced. Although the amino acid sequence identity between the four echotoxins and actinoporins
(20 kDa hemolysins from sea anemones) was very low (12–16%), some amino acid residues important for the biological activity
of actinoporins were well conserved in the echotoxins. In the case of echotoxin 2, the genomic DNA corresponding to the coding
region was amplified. Sequencing data revealed that the echotoxin 2 gene is devoid of introns within the coding region as
reported for the actinoporin genes. These results suggest that echotoxins have evolved from actinoporins or both toxins have
evolved from the same ancestor. 相似文献
82.
Ishikawa K Asahara T Gunji Y Yasueda H Asano K 《Bioscience, biotechnology, and biochemistry》2008,72(5):1317-1324
Methionine auxotrophic mutants of Methylophilus methylotrophus AS1 expressing a mutant form of dapA (dapA24) encoding a dihydrodipicolinate synthase desensitized from feedback inhibition by L-lysine, and mutated lysE (lysE24) encoding the L-lysine exporter from Corynebacterium glutamicum 2256, produced higher amounts of L-lysine from methanol as sole carbon source than did other amino acid auxotrophic mutants. Especially, the M. methylotrophus 102 strain, carrying both dapA24 and lysE24, produced L-lysine in more than 1.5 times amounts higher than the parent. A single-base substitution was identified in this auxotroph in codon-329 of the open reading frame of metF, encoding 5,10-methylene-tetra-hydrofolate reductase. We constructed a metF disruptant mutant carrying both dapA24 and lysE24, and confirmed increases in L-lysine production. This is the first report to the effect that metF deficient increased L-lysine production in methylotroph. 相似文献
83.
Ishikawa K Gunji Y Yasueda H Asano K 《Bioscience, biotechnology, and biochemistry》2008,72(10):2535-2542
To improve the amino acid production by metabolic engineering, eliminating the pathway bottleneck is known to be very effective. The metabolic response of Methylophilus methylotrophus upon the addition of glucose and of pyruvate was investigated in batch cultivation. We found that the supply of pyruvate is a bottleneck in L-lysine production in M. methylotrophus from methanol as carbon source. M. methylotrophus has a ribulose monophosphate (RuMP) pathway for methanol assimilation, and consequently synthesized fructose-6-phosphate is metabolized to pyruvate via the Entner-Doudoroff (ED) pathway, and the ED pathway is thought to be the main pathway for pyruvate supply. An L-lysine producer of M. methylotrophus with an enhanced ED pathway was constructed by the introduction of the E. coli edd-eda operon encoding the enzyme involving the ED pathway. In this strain, the overall enzymatic activity of ED pathway, which is estimated by measuring the activities of 6-phosphogluconate dehydrogenase plus 2-keto-3-deoxy-6-phosphogluconate aldolase, was about 20 times higher than in the parent. This strain produced 1.2 times more L-lysine than the parent producer. Perhaps, then, the supply of pyruvate was a bottleneck in L-lysine production in the L-lysine producer of M. methylotrophus. 相似文献
84.
Irie O Yokokawa F Ehara T Iwasaki A Iwaki Y Hitomi Y Konishi K Kishida M Toyao A Masuya K Gunji H Sakaki J Iwasaki G Hirao H Kanazawa T Tanabe K Kosaka T Hart TW Hallett A 《Bioorganic & medicinal chemistry letters》2008,18(16):4642-4646
We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of the inhibitors consist of a combination of a spiro[2.5]oct-6-ylmethylamine P2 group at the 4-position, a small or polar P3 group at the 5-position and/or a polar group at the 6-position of the pyrimidine. 相似文献
85.
Kurita S Watanabe Y Gunji E Ohashi K Mizuno K 《The Journal of biological chemistry》2008,283(47):32542-32552
Slingshot-1 (SSH1), a member of a dual-specificity protein phosphatase family, regulates actin dynamics by dephosphorylating and reactivating cofilin, an actin-depolymerizing factor. SSH1 has the SSH family-specific, N-terminal, noncatalytic (SSH-N) domain, consisting of the A and B subdomains. SSH1 is activated by binding to actin filaments. In this study, we examined the mechanisms of SSH1 substrate recognition of phospho-cofilin (P-cofilin) and SSH1 activation by F-actin. We found that P-cofilin binds to a phosphatase-inactive mutant, SSH1(CS), in which the catalytic Cys-393 is replaced by Ser. Using a series of deletion mutants, we provided evidence that both the phosphatase (P) domain and the adjacent B domain are indispensable for P-cofilin binding of SSH1(CS) and cofilin-phosphatase activity of SSH1. In contrast, the A domain is required for the F-actin-mediated activation of SSH1, but not for P-cofilin binding or basal cofilin-phosphatase activity. The P domain alone is sufficient for the phosphatase activity toward p-nitrophenyl phosphate (pNPP), indicating that the SSH-N domain is not essential for the basal phosphatase activity of SSH1. Addition of F-actin increased the cofilin-phosphatase activity of SSH1 more than 1200-fold, but the pNPP-phosphatase activity only 2.2-fold, which suggests that F-actin principally affects the cofilin-specific phosphatase activity of SSH1. When expressed in cultured cells, SSH1, but not its mutant deleted of SSH-N, accumulated in the rear of the lamellipodium. Together, these findings suggest that the conserved SSH-N domain plays critical roles in P-cofilin recognition, F-actin-mediated activation, and subcellular localization of SSH1. 相似文献
86.
Megu Gunji Masaki Fujita Hiroyoshi Higuchi 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2013,199(8):703-709
Most birds show a characteristic head movement that consists of head stabilization and quick displacement. In this movement, which is analogous to saccadic eye movement in mammals, head stabilization plays an important role in stabilizing the retinal image. This head movement, called “head bobbing”, is particularly pronounced during walking. Previous studies focusing on anatomical and behavioral features have pointed out that visual information is also important for diving birds, indicating its significance in the head movements of diving birds. In the present study, the kinematic and behavioral features of head bobbing in diving little grebes were described by motion analysis to identify the head movement in diving birds. The results showed that head-bobbing stroke (HBS) consisted of a thrust phase and a hold phase as is typical for head bobbing during walking birds. This suggests that HBS is related to visual stabilization under water. In HBS, grebes tended to dive with longer stroke length and smaller stroke frequency than in non-bobbing stroke. This suggests that the behavior, which is related to vision, affects the kinematic stroke parameters. This clarification of underwater head movement will help in our understanding not only of vision, but also of the kinematic strategy of diving birds. 相似文献
87.
H Shirai A R Poetsch A Gunji D Maeda H Fujimori H Fujihara T Yoshida H Ogino M Masutani 《Cell death & disease》2013,4(6):e656
Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for the degradation of poly(ADP-ribose). PARG dysfunction sensitizes cells to alkylating agents and induces cell death; however, the details of this effect have not been fully elucidated. Here, we investigated the mechanism by which PARG deficiency leads to cell death in different cell types using methylmethanesulfonate (MMS), an alkylating agent, and Parg−/− mouse ES cells and human cancer cell lines. Parg−/− mouse ES cells showed increased levels of γ-H2AX, a marker of DNA double strand breaks (DSBs), accumulation of poly(ADP-ribose), p53 network activation, and S-phase arrest. Early apoptosis was enhanced in Parg−/− mouse ES cells. Parg−/− ES cells predominantly underwent caspase-dependent apoptosis. PARG was then knocked down in a p53-defective cell line, MIAPaCa2 cells, a human pancreatic cancer cell line. MIAPaCa2 cells were sensitized to MMS by PARG knockdown. Enhanced necrotic cell death was induced in MIAPaCa2 cells after augmenting γ-H2AX levels and S-phase arrest. Taken together, these data suggest that DSB repair defect causing S-phase arrest, but p53 status was not important for sensitization to alkylation DNA damage by PARG dysfunction, whereas the cell death pathway is dependent on the cell type. This study demonstrates that functional inhibition of PARG may be useful for sensitizing at least particular cancer cells to alkylating agents. 相似文献
88.
Aquaporins (AQP) 1, 2, 3 and 4 belong to the aquaporin water channel family and play an important role in urine concentration by reabsorption of water from renal tubule fluid. Renal AQPs have not been reported in the yak (Bos grunniens), which resides in the Qinghai Tibetan Plateau. We investigated AQPs 1?4 expressions in the kidneys of Yak using immunohistochemical staining. AQP1 was expressed mainly in the basolateral and apical membranes of the proximal tubules and descending thin limb of the loop of Henle. AQP2 was detected in the apical plasma membranes of collecting ducts and distal convoluted tubules. AQP3 was located in the proximal tubule, distal tubule and collecting ducts. AQP4 was located in the collecting ducts, distal straight tubule, glomerular capillaries and peritubular capillaries. The expression pattern of AQPs 1?4 in kidney of yak was different from other species, which possibly is related to kidney function in a high altitude environment. 相似文献
89.
Shinichi Oide Wataru Gunji Yasuhiro Moteki Shogo Yamamoto Masako Suda Toru Jojima Hideaki Yukawa Masayuki Inui 《Applied and environmental microbiology》2015,81(7):2284-2298
Reinforcing microbial thermotolerance is a strategy to enable fermentation with flexible temperature settings and thereby to save cooling costs. Here, we report on adaptive laboratory evolution (ALE) of the amino acid-producing bacterium Corynebacterium glutamicum under thermal stress. After 65 days of serial passage of the transgenic strain GLY3, in which the glycolytic pathway is optimized for alanine production under oxygen deprivation, three strains adapted to supraoptimal temperatures were isolated, and all the mutations they acquired were identified by whole-genome resequencing. Of the 21 mutations common to the three strains, one large deletion and two missense mutations were found to promote growth of the parental strain under thermal stress. Additive effects on thermotolerance were observed among these mutations, and the combination of the deletion with the missense mutation on otsA, encoding a trehalose-6-phosphate synthase, allowed the parental strain to overcome the upper limit of growth temperature. Surprisingly, the three evolved strains acquired cross-tolerance for isobutanol, which turned out to be partly attributable to the genomic deletion associated with the enhanced thermotolerance. The deletion involved loss of two transgenes, pfk and pyk, encoding the glycolytic enzymes, in addition to six native genes, and elimination of the transgenes, but not the native genes, was shown to account for the positive effects on thermal and solvent stress tolerance, implying a link between energy-producing metabolism and bacterial stress tolerance. Overall, the present study provides evidence that ALE can be a powerful tool to refine the phenotype of C. glutamicum and to investigate the molecular bases of stress tolerance. 相似文献
90.