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991.
992.
Achim Schnaufer Meiting Wu Young-jun Park Tadashi Nakai Junpeng Deng Rose Proff Wim G. J. Hol Kenneth D. Stuart 《The Journal of biological chemistry》2010,285(8):5282-5295
Mitochondrial mRNA editing in trypanosomatid parasites involves several multiprotein assemblies, including three very similar complexes that contain the key enzymatic editing activities and sediment at ∼20S on glycerol gradients. These ∼20S editosomes have a common set of 12 proteins, including enzymes for uridylyl (U) removal and addition, 2 RNA ligases, 2 proteins with RNase III-like domains, and 6 proteins with predicted oligonucleotide binding (OB) folds. In addition, each of the 3 distinct ∼20S editosomes contains a different RNase III-type endonuclease, 1 of 3 related proteins and, in one case, an additional exonuclease. Here we present a protein-protein interaction map that was obtained through a combination of yeast two-hybrid analysis and subcomplex reconstitution with recombinant protein. This map interlinks ten of the proteins and in several cases localizes the protein region mediating the interaction, which often includes the predicted OB-fold domain. The results indicate that the OB-fold proteins form an extensive protein-protein interaction network that connects the two trimeric subcomplexes that catalyze U removal or addition and RNA ligation. One of these proteins, KREPA6, interacts with the OB-fold zinc finger protein in each subcomplex that interconnects their two catalytic proteins. Another OB-fold protein, KREPA3, appears to link to the putative endonuclease subcomplex. These results reveal a physical organization that underlies the coordination of the various catalytic and substrate binding activities within the ∼20S editosomes during the editing process. 相似文献
993.
Endo Satoru Takada Masashi Tanaka Hiroki Onizuka Yoshihiko Tanaka Kenichi Miyahara Nobuyuki Baba Hiromi Oishi Ayumu Ishikawa Masayori Hoshi Masaharu Kimura Shinzo Minematsu Masakazu Morimune Yuki Kojima Yasuaki Shizuma Kiyoshi 《Radiation and environmental biophysics》2010,49(3):469-475
Radiation and Environmental Biophysics - This study describes measurements on secondary particles produced by a 290 MeV/n Spread Out Bragg Peak (SOBP) carbon beam. Microdosimetric... 相似文献
994.
Takako Sasaki Junichi Takagi Camilla Giudici Yoshihiko Yamada Eri Arikawa-Hirasawa Rainer Deutzmann Rupert Timpl Arnoud Sonnenberg Hans Peter Bächinger David Tonge 《Matrix biology》2010,29(6):484-493
Laminin-121, previously referred as to laminin-3, was expressed recombinantly in human embryonic kidney (HEK) 293 cells by triple transfection of full-length cDNAs encoding mouse laminin α1, β2 and γ1 chains. The recombinant laminin-121 was purified using Heparin-Sepharose followed by molecular sieve chromatography and shown to be correctly folded by electron microscopy and circular dichroism (CD). The CD spectra of recombinant laminin-121 were very similar to those of laminin-111 isolated from Engelbreth-Holm-Swarm tumor (EHS-laminin) but its Tm value was smaller than EHS-laminin and recombinant lamnin-111 suggesting that the replacement of the β chain reduced the stability of the coiled-coil structure of laminin-121. Its binding to integrins was compared with EHS-laminin, laminin-3A32 purified from murine epidermal cell line and recombinantly expressed laminins-111, -211 and -221. Laminin-121 showed the highest affinity to α6β1 and α7β1 integrins and furthermore, laminin-121 most effectively supported neurite outgrowth. Together, this suggests that the β2 laminins have higher affinity for integrins than the β1 laminins. 相似文献
995.
Yoshihiko Shimokawa Hiroyuki Morita Ikuro Abe 《Bioorganic & medicinal chemistry letters》2010,20(17):5099-5103
Benzalacetone synthase (BAS) and chalcone synthase (CHS) are plant-specific type III polyketide synthases (PKSs), sharing 70% amino acid sequence identity and highly homologous overall protein structures. BAS catalyzes the decarboxylative coupling of 4-coumaroyl-CoA with malonyl-CoA to produce the diketide benzalacetone, whereas CHS produces the tetraketide chalcone by iterative condensations with three molecules of malonyl-CoA, and folding the resulting intermediate into a new aromatic ring system. Recent crystallographic analyses of Rheum palmatum BAS revealed that the characteristic substitution of Thr132 (numbering of Medicago sativa CHS2), a conserved CHS residue lining the active-site cavity, with Leu causes steric contraction of the BAS active-site to produce the diketide, instead of the tetraketide. To test this hypothesis, we constructed a set of R. palmatum BAS site-directed mutants (L132G, L132A, L132S, L132C, L132T, L132F, L132Y, L132W and L132P), and investigated the mechanistic consequences of the point mutations. As a result, the single amino acid substitution L132T restored the chalcone-forming activity in BAS, whereas the Ala, Ser, and Cys substitutions expanded the product chain length to produce 4-coumaroyltriacetic acid lactone (CTAL) after three condensations with malonyl-CoA, but without the formation of the aromatic ring system. Homology modeling suggested that this is probably caused by the restoration of the ‘coumaroyl binding pocket’ in the active-site cavity. These findings provide further insights into the structural details of the catalytic mechanism of the type III PKS enzymes. 相似文献
996.
Rena Nishizawa Toshihiko Nishiyama Katsuya Hisaichi Keisuke Hirai Hiromu Habashita Yoshikazu Takaoka Hideaki Tada Kenji Sagawa Shiro Shibayama Kenji Maeda Hiroaki Mitsuya Hisao Nakai Daikichi Fukushima Masaaki Toda 《Bioorganic & medicinal chemistry》2010,18(14):5208-5223
Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti-HIV activity. Full details of structure–activity relationship (SAR) study are presented. 相似文献
997.
Masaki Asada Maki Iwahashi Tetsuo Obitsu Atsushi Kinoshita Yoshihiko Nakai Takahiro Onoda Toshihiko Nagase Motoyuki Tanaka Yoshiyuki Yamaura Hiroya Takizawa Ken Yoshikawa Kazutoyo Sato Masami Narita Shuichi Ohuchida Hisao Nakai Masaaki Toda 《Bioorganic & medicinal chemistry》2010,18(4):1641-1658
A series of 3-[2-{[(3-methyl-1-phenylbutyl)amino]carbonyl}-4-(phenoxymethyl)phenyl]propanoic acid analogs were synthesized and evaluated for their in vitro potency. In most cases, introduction of one or two substituents into the two phenyl moieties resulted in the tendency of an increase or retention of in vitro activities. Several compounds, which showed excellent subtype selectivity, were evaluated for their inhibitory effect against PGE2-induced uterine contraction in pregnant rats, which is thought to be mediated by the EP3 receptor subtype. The structure–activity relationships (SARs) are also discussed. 相似文献
998.
999.
Nobumitsu Kobayashi Masayuki Hanaoka Yunden Droma Michiko Ito Yoshihiko Katsuyama Keishi Kubo Masao Ota 《PloS one》2013,8(8)
Introduction
High-altitude pulmonary edema (HAPE) is a hypoxia-induced, life-threatening, high permeability type of edema attributable to pulmonary capillary stress failure. Genome-wide association analysis is necessary to better understand how genetics influence the outcome of HAPE.Materials and Methods
DNA samples were collected from 53 subjects susceptible to HAPE (HAPE-s) and 67 elite Alpinists resistant to HAPE (HAPE-r). The genome scan was carried out using 400 polymorphic microsatellite markers throughout the whole genome in all subjects. In addition, six single nucleotide polymorphisms (SNPs) of the gene encoding the tissue inhibitor of metalloproteinase 3 (TIMP3) were genotyped by Taqman® SNP Genotyping Assays.Results
The results were analyzed using case-control comparisons. Whole genome scanning revealed that allele frequencies in nine markers were statistically different between HAPE-s and HAPE-r subjects. The SNP genotyping of the TIMP3 gene revealed that the derived allele C of rs130293 was associated with resistance to HAPE [odds ratio (OR) = 0.21, P = 0.0012) and recessive inheritance of the phenotype of HAPE-s (P = 0.0012). A haplotype CAC carrying allele C of rs130293 was associated with resistance to HAPE.Discussion
This genome-wide association study revealed several novel candidate genes associated with susceptibility or resistance to HAPE in a Japanese population. Among those, the minor allele C of rs130293 (C/T) in the TIMP3 gene was linked to resistance to HAPE; while, the ancestral allele T was associated with susceptibility to HAPE. 相似文献1000.
M. J. Park Joseph Green Hirono Ishikawa Yoshihiko Yamazaki Akira Kitagawa Miho Ono Fumiko Yasukata Takahiro Kiuchi 《PloS one》2013,8(6)