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121.
In eukaryotic DNA replication, replication factor-C (RFC) acts as the clamp loader, which correctly installs the sliding clamp onto DNA strands at replication forks. The eukaryotic RFC is a complex consisting of one large and four small subunits. We have determined the crystal structure of the clamp loader small subunit (RFCS) from Pyrococcus furiosus. The six subunits, of which four bind ADP in their canonical nucleotide binding clefts, assemble into a dimer of semicircular trimers. The crescent-like architecture of each subunit formed by the three domains resembles that of the delta' subunit of the E. coli clamp loader. The trimeric architecture of archaeal RFCS, with its mobile N-terminal domains, involves intersubunit interactions that may be conserved in eukaryotic functional complexes. 相似文献
122.
A new procedure to accurately measure a trace amount of d-proline in biological samples has been developed. This D-amino acid was derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole and was determined by a column-switching HPLC system, a combination of a micro-ODS column and a chiral column. The detection limit for D-proline spiked in a mouse cerebrum sample is 1 fmol (injection amount, S/N = 3). Within-day precision and day-to-day precision obtained for spiked d-proline (10 fmol) are 2.14 and 5.35% (RSD), respectively. Using the new method, the amount of free D-proline in eight brain regions and sera of mutant ddY/DAO- mice, lacking D-amino acid oxidase activity, and control ddY/DAO+ mice was determined. The amount of free D-leucine was also investigated. The amount and distribution of D-proline in the brains of ddY/DAO+ mice and ddY/DAO- mice are almost the same, and relatively high amounts of D-proline have been observed in the pituitary gland and in the pineal gland. On the other hand, the amount of D-leucine is different between the two strains. In the brains of ddY/DAO+ mice, a relatively high amount of D-leucine has been observed in the pineal gland compared with other regions. In the brains of ddY/DAO- mice, D-leucine amounts are approximately 10 times higher than those obtained in ddY/DAO+ mice and regional difference has not been observed, while the amounts of L-proline and L-leucine are not significantly different between the two strains. In the serum, the amounts of both free D-proline and d-leucine are significantly higher in the ddY/DAO- mice than those obtained in ddY/DAO+ mice. 相似文献
123.
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125.
S Ogawa S Uetsuki Y Tezuka T Morikawa A Takahashi K Sato 《Bioorganic & medicinal chemistry letters》1999,9(11):1493-1498
Twelve 1,2- and 2,3-anhydro-1,2,3,4,5-cyclohexanepentols were synthesized from (+)-epi- and (-)-vibo-quercitols, readily available by bioconversion of myo-inositol, and assayed for inhibitory activity against glucocerebrosidase (mouse liver). Among them 1L-1,2-anhydro-1,2,4/3,5-cyclohexanepentol, the 3-deoxy derivative of the irreversible inhibitor conduritol B epoxide (CBE), has been demonstrated to be a highly potent and specific inhibitor, almost comparable to the parent compound. 相似文献
126.
Escherichia coli esterase (EcE) is a member of the hormone-sensitive lipase family. We have analyzed the roles of the conserved residues in this enzyme (His103, Glu128, Gly163, Asp164, Ser165, Gly167, Asp262, Asp266 and His292) by site-directed mutagenesis. Among them, Gly163, Asp164, Ser165, and Gly167 are the components of a G-D/E-S-A-G motif. We showed that Ser165, Asp262, and His292 are the active-site residues of the enzyme. We also showed that none of the other residues, except for Asp164, is critical for the enzymatic activity. The mutation of Asp164 to Ala dramatically reduced the catalytic efficiency of the enzyme by the factor of 10(4) without seriously affecting the substrate binding. This residue is probably structurally important to make the conformation of the active-site functional. 相似文献
127.
S Mizuguchi K Amada M Haruki T Imanaka M Morikawa S Kanaya 《Journal of biochemistry》1999,126(4):731-737
The gene encoding an esterase (HDE) was cloned from an oil-degrading bacterium, strain HD-1. HDE is a member of the hormone-sensitive lipase family and composed of 317 amino acid residues with a molecular weight of 33,633. The HDE-encoding gene was expressed in Escherichia coli, and the recombinant protein was purified and characterized. Amino acid sequence analysis indicated that the methionine residue was removed from its NH(2)-terminus. The good agreement of the molecular weights estimated by SDS-PAGE (35,000) and gel filtration (38,000) suggests that it acts in a monomeric form. HDE showed hydrolytic activity towards p-nitrophenyl esters of fatty acids with an acyl chain length of 2 to 14 and tributyrin, whereas it showed little hydrolytic activity towards p-nitrophenyl oleate (C(18)), tricaprylin and triolein. Determination of the kinetic parameters for the hydrolyses of the p-nitrophenyl substrates from C(2) to C(14) indicated that HDE shows a relatively broad substrate specificity. However, comparison of the k(cat)/K(m) values indicated that the C(10)-C(14) substrates are the most preferred ones. Such a preference for substrates with long acyl chains may be a characteristic of HDE. 相似文献
128.
M. Kato Toshiyuki Kimura Changqing Lin Aiko Ito Soichi Kodama Tateki Morikawa Takashi Soga Kiyoshi Hayasaka 《Human genetics》1999,104(4):341-344
The doublecortin (DCX) gene was recently found to be involved in patients with X-linked lissencephaly and subcortical band
heterotopia or double cortex syndrome. We have studied the coding regions of the DCX gene in 11 Japanese patients with cortical
dysplasia and have identified three different mutations (R186C in exon 3, R272X and R303X in exon 5) in four sporadic female
cases. R272X, which has been detected in two unrelated cases, is a novel mutation. Although the number of cases studied remains
limited, exon 5 may be a common mutational site in Japanese patients in contrast to many previus reports concerning exons
2 and 3.
Received: 28 October 1998 / Accepted: 26 February 1999 相似文献
129.
Developmental processes of the fetal rat kidney from uninephrectomized mothers were studied. The uninephrectomy was performed on day 5 of gestation. Glomerular number and volume in the fetal kidneys on days 18, 20, and 22 of gestation were morphometrically determined. To investigate the anionic site formation in the glomerular basement membrane, distribution of cationized ferritin (CF) in the fetal glomerulus was examined electron microscopically after CF injection. Blood urea nitrogen (BUN) concentration in the pregnant rats was also determined on various days after uninephrectomy. On fetal days 20 and 22, the glomerular volume was significantly larger in the fetuses from uninephrectomized mothers than in those from sham-operated ones. On fetal day 20, the CF particles were clustered in the laminae rarae interna and externa of the glomerular basement membrane in the fetuses from uninephrectomized mothers, while the clusters were arrayed in three to four layers in the glomerular basement membrane in the fetuses from sham-operated ones. On fetal day 22, the CF particles noted in the lamina rara externa in the fetuses from uninephrectomized mothers were slightly larger in number than such particles in the age-matched control fetuses. The BUN concentration of the uninephrectomized pregnant rats was significantly higher than that of the sham-operated pregnant ones on each postoperative day. These results suggest that the development of the fetal renal glomerulus is accelerated by the elevated BUN level following maternal uninephrectomy when the fetal kidney is functional in effective filtration in the rat. J. Morphol. 238:337–342, 1998. © 1998 Wiley-Liss, Inc. 相似文献
130.
Kasuga J Oyama T Hirakawa Y Makishima M Morikawa K Hashimoto Y Miyachi H 《Bioorganic & medicinal chemistry letters》2008,18(16):4525-4528
We developed a potent peroxisome proliferator-activated receptor pan agonist (a candidate drug for treatment of altered metabolic homeostasis) by introducing fluorine atoms at appropriate position(s) of the known phenylpropionic acid-type pan agonist TIPP-703. 相似文献