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141.
142.
Koichi Kobayashi Nobuyoshi Mochizuki Naho Yoshimura Ken Motohashi Toru Hisabori Tatsuru Masuda 《Photochemical & photobiological sciences》2008,7(10):1188-1195
The first step of chlorophyll biosynthesis is catalyzed by a Mg-chelatase composed of the subunits CHLI, CHLD and CHLH. Mg-chelatase requires ATP hydrolysis that can be attributed to CHLI. Arabidopsis has two CHLI isoforms, CHLI1 and CHLI2, that have similar expression profiles, but it has been suggested that CHLI2 has limited function in the Mg-chelatase complex. Recently, we showed that Arabidopsis CHLI1 is an ATPase and a target of chloroplast thioredoxin. Here, we demonstrate that CHLI2 also has ATPase activity but with a lower Vmax and higher Km ATP than CHLI1. We confirmed the thioredoxin-dependent reduction of a disulfide bond in CHLI2 and thiol-modulation of its ATPase activity. We then examined the physiological contribution of CHLI2 using a chli2 T-DNA knockout line. Although visible phenotype of homozygous chli2 mutants was almost comparable to wild type, the mutant accumulated significantly less chlorophyll. Furthermore, cs/cs; chli2/chli2 double mutants were almost albino. There were three phenotypes among progenies segregated from the cs/cs; CHLI2/chli2 parent: cs-like pale green, yellow, and almost albino were obtained in the approximate ratio of 1:2:0.7. PCR analysis confirmed that the chli2 mutation is semidominant on a homozygous cs background. These results reveal that although CHLI2 plays a limited role in chlorophyll biosynthesis, this subunit certainly contributes to the assembly of the Mg-chelatase complex. 相似文献
143.
Juliano R. Guerreiro Claudiana Lameu Eduardo F. Oliveira Cl��cio F. Klitzke Robson L. Melo Edlaine Linares Ohara Augusto Jay W. Fox Ivo Lebrun Solange M. T. Serrano Antonio C. M. Camargo 《The Journal of biological chemistry》2009,284(30):20022-20033
Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-de pend ent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, α-methyl-dl-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases.Inhibition of somatic angiotensin-I-converting enzyme (sACE)3 is a widely used approach in the treatment of hypertension. The first available competitive inhibitors of sACE were the naturally occurring proline-rich oligopeptides from the venom of Bothrops jararaca. Clinical studies using Bj-BPP-9a, teprotide, the most efficient of these snake venom peptides, demonstrated the potential of sACE inhibitors as anti-hypertensive drugs (1). Highly potent inhibitors of sACE, which can be administered orally, have subsequently been developed. The first of these, captopril, was designed employing a theoretical model of the active site of sACE, based on its presumed similarity to the active site of carboxypeptidase A and also with reference to the C terminus of venom proline-rich peptides, which compete with sACE substrates (2). Since captopril reproduced all known pharmacological effects and sACE-inhibiting features of the proline-rich peptides (3), the interest to deepen the investigation of the biological properties of these naturally occurring sACE inhibitors dropped dramatically. However, we recently showed that the Bj-BPP-10c (4), displays a strong and sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), independently of the inhibition of sACE (5). This result led us to hypothesize that, besides sACE, another molecule involved in the arterial blood pressure homeostasis could possibly be a target for Bj-BPP-10c. Two reasons prompted us to search the putative target in the kidney: (i) the crucial role played by the kidney in the arterial blood pressure control (6) and (ii) the selective concentration and long lasting permanence of 125I-Bj-BPP-10c in the mouse kidney even when a saturating concentration of captopril was administered with the peptide (7).In the present study, we identified the kidney argininosuccinate synthetase (AsS) as a putative target for Bj-BPP10c, and we show results demonstrating that the anti-hypertensive effect of this peptide in SHR is related to the activation of the arginine production in the kidney and of the citrulline-NO cycle in endothelial cells. 相似文献
144.
Takatomo Fujisawa Rei Narikawa Shinobu Okamoto Shigeki Ehira Hidehisa Yoshimura Iwane Suzuki Tatsuru Masuda Mari Mochimaru Shinichi Takaichi Koichiro Awai Mitsuo Sekine Hiroshi Horikawa Isao Yashiro Seiha Omata Hiromi Takarada Yoko Katano Hiroki Kosugi Satoshi Tanikawa Kazuko Ohmori Naoki Sato Masahiko Ikeuchi Nobuyuki Fujita Masayuki Ohmori 《DNA research》2010,17(2):85-103
145.
Suzuki M Yanagawa Y Iwasaki H Kanda H Yanagihara K Matsumoto H Ohara Y Yazaki Y Sakoda R 《Bioorganic & medicinal chemistry letters》1999,9(20):2977-2982
First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104 are reported. A pair of syn diol isomers (NK-104 and its enantiomer) was obtained efficiently by diastereomeric resolution. The synthesis of a pair of anti diol isomers (3-epimer and 5-epimer) was accomplished effectively by the asymmetric aldol reaction followed by anti stereoselective reduction as key steps. Their purity determinations were effected by chiral HPLC analysis. 相似文献
146.
Kazuhiro Ohara Hideaki Unno Yasuhiro Oshima Miho Hosoya Naoto Fujino Kazutake Hirooka Seiji Takahashi Satoshi Yamashita Masami Kusunoki Toru Nakayama 《The Journal of biological chemistry》2014,289(35):24499-24510
To investigate the mechanism for low pH adaptation by a carboxylesterase, structural and biochemical analyses of EstFa_R (a recombinant, slightly acidophilic carboxylesterase from Ferroplasma acidiphilum) and SshEstI (an alkaliphilic carboxylesterase from Sulfolobus shibatae DSM5389) were performed. Although a previous proteomics study by another group showed that the enzyme purified from F. acidiphilum contained an iron atom, EstFa_R did not bind to iron as analyzed by inductively coupled plasma MS and isothermal titration calorimetry. The crystal structures of EstFa_R and SshEstI were determined at 1.6- and 1.5-Å resolutions, respectively. EstFa_R had a catalytic triad with an extended hydrogen bond network that was not observed in SshEstI. Quadruple mutants of both proteins were created to remove or introduce the extended hydrogen bond network. The mutation on EstFa_R enhanced its catalytic efficiency and gave it an alkaline pH optimum, whereas the mutation on SshEstI resulted in opposite effects (i.e. a decrease in the catalytic efficiency and a downward shift in the optimum pH). Our experimental results suggest that the low pH optimum of EstFa_R activity was a result of the unique extended hydrogen bond network in the catalytic triad and the highly negatively charged surface around the active site. The change in the pH optimum of EstFa_R happened simultaneously with a change in the catalytic efficiency, suggesting that the local flexibility of the active site in EstFa_R could be modified by quadruple mutation. These observations may provide a novel strategy to elucidate the low pH adaptation of serine hydrolases. 相似文献
147.
148.
Shaham Beg Rohan Bareja Kentaro Ohara Kenneth Wha Eng David C. Wilkes David J. Pisapia Wael Al Zoughbi Sarah Kudman Wei Zhang Rema Rao Jyothi Manohar Troy Kane Michael Sigouros Jenny Zhaoying Xiang Francesca Khani Brian D. Robinson Bishoy M. Faltas Cora N. Sternberg Andrea Sboner Himisha Beltran Olivier Elemento Juan Miguel Mosquera 《Translational oncology》2021,14(1)
149.
150.
M Endoh TA Endo T Endoh K Isono J Sharif O Ohara T Toyoda T Ito R Eskeland WA Bickmore M Vidal BE Bernstein H Koseki 《PLoS genetics》2012,8(7):e1002774
Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3), respectively. Compared to H3K27me3, localization and the role of H2AK119u1 are not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation. 相似文献