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991.
Tanaka Y Doi S Kamiya N Kawata N Kamiya S Nakama K Goto M 《Biotechnology letters》2008,30(6):1025-1029
An amino-modified glass surface for enzymatic protein immobilization by microbial transglutaminase (MTG) was developed. Diamine
substrates with secondary amino groups in the linker moiety, like triethylenetetramine (TETA), exhibited at most a 2-fold
higher reactivity in the MTG-catalyzed reaction compared to those with the alkyl linker. A 96-well glass plate was subsequently
modified with selected diamine substrates. Validation of the modified surface by enzymatic immobilization of enhanced green
fluorescent protein tagged with a glutamine donor-substrate peptide (LLQG) of MTG revealed that the protein loading onto the
TETA-modified glass surface was approximately 15-fold higher than that on the unmodified one. 相似文献
992.
PixD/Slr1694 from the cyanobacterium Synechocystis sp. PCC6803 is a member of a new class of flavin-containing blue-light sensory proteins containing a BLUF (blue light using flavin) domain. The photocycle reaction mechanism of BLUF is unique because only small structural changes of a bound chromophore are accompanied by a few hydrogen bond rearrangements in the chromophore-binding site. Here, we show that in PixD, Met93, the residue conserved in all BLUF domains, is crucial for light-dependent signal transduction. Specifically, the light-insensitive M93A mutant of PixD revealed biochemical and physiological activities compatible with those of the light-adapted wild-type PixD. However, the W91A mutant of PixD retained light sensitivity and biological function, although the corresponding mutant of another BLUF protein, AppA, has been reported to be locked in the light signaling state. These observations suggest that the pathway through which the light signal is transformed into apoprotein structural changes has been modified in BLUF proteins for their respective functions. 相似文献
993.
The two-process model is a scheme for the timing of sleep that consists of homeostatic (Process S) and circadian (Process
C) variables. The two-process model exhibits abnormal sleep patterns such as internal desynchronization or sleep fragmentation.
Early infants with autism often experience sleep difficulties. Large day-by-day changes are found in the sleep onset and waking
times in autistic children. Frequent night waking is a prominent property of their sleep. Further, the sleep duration of autistic
children is often fragmented. These sleep patterns in infants with autism are not fully understood yet. In the present study,
the sleep patterns in autistic children were reproduced by a modified two-process model using nonlinear analysis. A nap term
was introduced into the original two-process model to reproduce the sleep patterns in early infants. The nap term and the
time course of Process S are mentioned in the present study. Those parameters led to bifurcation of the sleep-wake cycle in
the modified two-process model. In a certain range of these parameter sets, a small external noise was amplified, and an irregular
sleep-wake cycle appeared. The short duration of sleep led to another irregular sleep onset or waking. Consequently, an irregular
sleep-wake cycle appeared in early infantile autism. 相似文献
994.
Toshiyuki Fukada Natacha Civic Tatsuya Furuichi Shinji Shimoda Kenji Mishima Hiroyuki Higashiyama Yayoi Idaira Yoshinobu Asada Hiroshi Kitamura Satoru Yamasaki Shintaro Hojyo Manabu Nakayama Osamu Ohara Haruhiko Koseki Heloisa G. dos Santos Luisa Bonafe Russia Ha-Vinh Andreas Zankl Sheila Unger Marius E. Kraenzlin Jacques S. Beckmann Ichiro Saito Carlo Rivolta Shiro Ikegawa Andrea Superti-Furga Toshio Hirano 《PloS one》2008,3(11)
Background
Zinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown.Methodology/Principal Findings
Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS). The Slc39a13 knockout (Slc39a13-KO) mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP) and TGF-β signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice.Conclusions/Significance
Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-β signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-β signaling and connective tissue dysfunction. 相似文献995.
Shinji Takenaka Takahiro Ozeki Kosei Tanaka Ken-ichi Yoshida 《Biotechnology letters》2017,39(11):1699-1707
Objectives
To predict the amino acid residues playing important roles in acetyl-CoA and substrate binding and to study the acetyl group transfer mechanism of Chryseobacterium sp. 5-3B N-acetyltransferase (5-3B NatA).Results
A 3-dimensional homology model of 5-3B NatA was constructed to compare the theoretical structure of this compound with the structures of previously reported proteins belonging to the bacterial GCN5 N-acetyltransferase family. Homology modeling of the 5-3B NatA structure and a characterization of the enzyme’s kinetic parameters identified the essential amino acid residues involved in binding and acetyl-group transfer. 126Leu, 132Leu, and 135Lys were implicated in the binding of phosphopantothenic acid, and 100Tyr and 131Lys in that of adenosyl biphosphate. The data supported the participation of 83Glu and 133Tyr in catalyzing acetyl-group transfer to l-2-phenylglycine.Conclusions
5-3B NatA catalyzes the enantioselective N-acetylation of l-2-phenylglycine via a ternary complex comprising the enzyme, acetyl-CoA, and the substrate.996.
Takanobu Jotatsu Shigehiro Yagishita Ken Tajima Fumiyuki Takahashi Kaoru Mogushi Moulid Hidayat Aditya Wirawan Ryo Ko Ryota Kanemaru Naoko Shimada Keiko Mitani Tsuyoshi Saito Kazuya Takamochi Kenji Suzuki Shinji Kohsaka Shinya Kojima Hiroshi Mukae Kazuhiro Yatera Kazuhisa Takahashi 《Biochemistry and Biophysics Reports》2017
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by rapid progression. The mechanisms that lead to a shift from initial therapeutic sensitivity to ultimate therapeutic resistance are poorly understood. Although the SCLC genomic landscape led to the discovery of promising agents targeting genetic alterations that were already under investigation, results have been disappointing. Achievements in targeted therapeutics have not been observed for over 30 years. Therefore, the underlying disease biology and novel targets urgently require a better understanding. Epigenetic regulation is deeply involved in the cellular plasticity that could shift tumor cells to the malignant phenotype. We have focused on a histone modifier, LSD1, that is overexpressed in SCLC and is a potent therapeutic target. Interestingly, the LSD1 splice variant LSD1+8a, the expression of which has been reported to be restricted to neural tissue, was detected and was involved in the expression of neuroendocrine marker genes in SCLC cell lines. Cells with high expression of LSD1+8a were resistant to CDDP and LSD1 inhibitor. Moreover, suppression of LSD1+8a inhibited cell proliferation, indicating that LSD1+8a could play a critical role in SCLC. These findings suggest that LSD1+8a should be considered a novel therapeutic target in SCLC. 相似文献
997.
998.
Kosuke Anan Moriyasu Masui Shinichiro Hara Miho Ohara Masaharu Kume Shoichi Yamamoto Shunji Shinohara Hiroki Tsuji Shinji Shimada Shigenori Yagi Nobuyoshi Hasebe Hiroyuki Kai 《Bioorganic & medicinal chemistry letters》2017,27(17):4194-4198
NR2B subunit containing N-methyl-d-aspartate (NMDA) receptor is an attractive target for chronic pain due to its involvement in disease states and its limited distribution in the central nervous system. Cyclohexanol-based leads 6a and 6c were identified as potent NR2B-selective NMDA antagonists utilizing a scaffold hopping approach. Further optimization of this series through replacement of the amide in the leads with an isoxazole and efforts to optimize the pharmacokinetic profiles led to the discovery of orally available brain penetrants 7k and 7l, which demonstrated analgesic activity in the mouse formalin test at early and late phases. 相似文献
999.
Kentaro Igarashi Kei Kawaguchi Tasuku Kiyuna Takashi Murakami Shinji Miwa Scott D. Nelson 《Cell cycle (Georgetown, Tex.)》2017,16(1):91-94
Rhabdomyosarcoma (RMS) is a rare mesenchymal tumor. The aim of the present study was to develop a patient-derived orthotopic xenograft (PDOX) mouse model of RMS and compare the PDOX model to a subcutaneous (s.c.)-transplant model. A patient RMS from a striated muscle was grown orthotopically in the right biceps femoris muscle and right quadriceps muscle of nude mice to establish a PDOX model, as well as under the skin to establish an s.c. model. PDOX tumors grew at a statistically-significant faster rate compared to the s.c. tumors. Recurrence after surgical resection occurred only in PDOX tumors, not in the s.c. model. Histologically, only the PDOX model was shown to be invasive. In conclusion, these results indicate that the PDOX model of adult RMS is malignant and the subcutaneous model is benign. These results emphasize that a proper tumor microenvironment is necessary for patient-like behavior of a tumor in a mouse model. 相似文献
1000.
Koichi Orino Misaki Higa Mika Fujikawa Kazuhiro Takehara Shozo Okano Shinji Yamamoto Kiyotaka Watanabe 《Biometals》2002,15(2):161-165
Ferritin-binding proteins circulating in mammalian blood are thought to be involved in the clearance of ferritin. The present study characterizes canine serum autoantibodies (IgM and IgA) that react with ferritin. Canine IgM and IgA bound to bovine spleen ferritin as well as canine liver ferritin. To examine the specificity of canine IgM and IgA to ferritin H and L subunits, we used canine heart ferritin and canine liver ferritin with H/L subunit ratios of 3.69 and 0.43, respectively. Canine IgM and IgA recognized both of the H- and L-subunit-rich isoferritins, showing that their binding activities to ferritin depend on the H-subunit content. Recombinant bovine H-chain ferritin homopolymer expressed in a baculovirus expression system bound more with IgM and IgA than the recombinant L-chain homopolymer expressed under the same conditions. These results suggest that canine IgM and IgA recognize H-subunit-rich isoferritins, and that H-subunit-rich isoferritins are cleared from the circulation more rapidly than L-subunit-rich isoferritins. 相似文献