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81.
The eukaryotic integral membrane enzyme isoprenylcysteine carboxyl methyltransferase (ICMT) methylates the carboxylate of a lipid-modified cysteine at the C terminus of its protein substrates. This is the final post-translational modification of proteins containing a CAAX motif, including the oncoprotein Ras, and therefore, ICMT may serve as a therapeutic target in cancer development. ICMT has no discernible sequence homology with soluble methyltransferases, and aspects of its catalytic mechanism are unknown. For example, how both the methyl donor S-adenosyl-l-methionine (AdoMet), which is water-soluble, and the methyl acceptor isoprenylcysteine, which is lipophilic, are recognized within the same active site is not clear. To identify regions of ICMT critical for activity, we combined scanning mutagenesis with methyltransferase assays. We mutated nearly half of the residues of the ortholog of human ICMT from Anopheles gambiae and observed reduced or undetectable catalytic activity for 62 of the mutants. The crystal structure of a distantly related prokaryotic methyltransferase (Ma Mtase), which has sequence similarity with ICMT in its AdoMet binding site but methylates different substrates, provides context for the mutational analysis. The data suggest that ICMT and Ma MTase bind AdoMet in a similar manner. With regard to residues potentially involved in isoprenylcysteine binding, we identified numerous amino acids within transmembrane regions of ICMT that dramatically reduced catalytic activity when mutated. Certain substitutions of these caused substrate inhibition by isoprenylcysteine, suggesting that they contribute to the isoprenylcysteine binding site. The data provide evidence that the active site of ICMT spans both cytosolic and membrane-embedded regions of the protein. 相似文献
82.
Weimin Zhou Min Zhu Ming Gui Lihua Huang Zhi Long Li Wang Hui Chen Yinghao Yin Xianzhen Jiang Yingbo Dai Yuxin Tang Leye He Kuangbiao Zhong 《PloS one》2014,9(10)
Alterations of mitochondrial DNA (mtDNA) have been associated with the risk of a number of human cancers; however, the relationship between mtDNA copy number in peripheral blood leukocytes (PBLs) and the risk of prostate cancer (PCa) has not been investigated. In a case-control study of 196 PCa patients and 196 age-paired healthy controls in a Chinese Han population, the association between mtDNA copy number in PBLs and PCa risk was evaluated. The relative mtDNA copy number was measured using quantitative real-time PCR; samples from three cases and two controls could not be assayed, leaving 193 cases and 194 controls for analysis. PCa patients had significantly higher mtDNA copy numbers than controls (medians 0.91 and 0.82, respectively; P<0.001). Dichotomized at the median value of mtDNA copy number in the controls, high mtDNA copy number was significantly associated with an increased risk of PCa (adjusted odds ratio = 1.85, 95% confidence interval: 1.21–2.83). A significant dose-response relationship was observed between mtDNA copy number and risk of PCa in quartile analysis (Ptrend = 0.011). Clinicopathological analysis showed that high mtDNA copy numbers in PCa patients were significantly associated with high Gleason score and advanced tumor stage, but not serum prostate-specific antigen level (P = 0.002, 0.012 and 0.544, respectively). These findings of the present study indicate that increased mtDNA copy number in PBLs is significantly associated with an increased risk of PCa and may be a reflection of tumor burden. 相似文献
83.
Jiaqing Xiong Meng‐Fang Lin Jiangxin Wang Sheng Long Gaw Kaushik Parida Pooi See Lee 《Liver Transplantation》2017,7(21)
Realizing energy harvesting from water flow using triboelectric generators (TEGs) based on our daily wearable fabric or textile has practical significance. Challenges remain on methods to fabricate conformable TEGs that can be easily incorporated into waterproof textile, or directly harvest energy from water using hydrophobic textile. Herein, a wearable all‐fabric‐based TEG for water energy harvesting, with additional self‐cleaning and antifouling properties is reported for the first time. Hydrophobic cellulose oleoyl ester nanoparticles (HCOENPs) are prepared from microcrystalline cellulose, as a low‐cost and nontoxic coating material to achieve superhydrophobic coating on fabrics, including cotton, silk, flax, polyethylene terephthalate (PET), polyamide (nylon), and polyurethane. The resultant PET fabric‐based water‐TEG can generate an instantaneous output power density of 0.14 W m?2 at a load resistance of 100 MΩ. An all‐fabric‐based dual‐mode TEG is further realized to harvest both the electrostatic energy and mechanical energy of water, achieving the maximum instantaneous output power density of 0.30 W m?2. The HCOENPs‐coated fabric provides excellent breathability, washability, and environmentally friendly fabric‐based TEGs, making it a promising wearable self‐powered system. 相似文献
84.
Zhen Wang Li Ping Cheng Xing Hua Zhang Wan Pang Liang Li Jin Long Zhao 《Bioorganic & medicinal chemistry letters》2017,27(24):5429-5435
Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r2) and cross-validation coefficient (q2) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r2 and q2 of CoMSIA (comparative molecular similarity analysis) are 0.992 and 0.863, respectively. Molecular docking and MD simulations were conducted to confirm the detailed binding mode of enzyme-inhibitor system. The new NA inhibitors had been designed, synthesized, and their inhibitory activities against group-1 neuraminidase were determined. One agent displayed excellent neuraminidase inhibition, with IC50 value of 39.6?μM against NA, while IC50 value for oseltamivir is 61.1?μM. This compound may be further investigated for the treatment of infection by the new type influenza virus. 相似文献
85.
Meng Wu Shunyou Long Anthony G. Frutos Maryna Eichelberger Ye Fang 《Journal of receptor and signal transduction research》2013,33(3-4):202-210
The Epic® system, a high-throughput label-free optical biosensor system, is applied for the biochemical interrogation of phosphor-specific interactions of the 14-3-3 protein and its substrates. It has shown the capability not only for high-throughput characterization of binding rank and affinity but also for the exploration of potential interacting kinases for the substrates. A perspective of biochemical applications for diagnostics and biomarker discovery, as well as cell-based applications for endogenous receptors and viral infection characterization, are also provided. 相似文献
86.
87.
Xu Han Yun Long Yu Duo Ma Zhao Yan Zhang Xin Hua Liu 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):345
Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 < 1 µM), which was significantly superior to the staurosporine (IC50 = 6.41 µM). In addition, clear structure–activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase. 相似文献
88.
为揭示不同林龄沙地樟子松人工林土壤理化性质和微生物生物量的动态和相互关系,以毛乌素沙地、科尔沁沙地和呼伦贝尔沙地不同林龄樟子松人工林为对象,分析土壤理化性质、土壤微生物生物量碳和微生物生物量氮变化规律。结果表明:樟子松人工林土壤理化性质随林龄增加在不同沙地中表现不同,毛乌素沙地土壤容重和养分含量明显降低,科尔沁沙地土壤孔隙度和养分含量明显升高,呼伦贝尔沙地土壤养分则呈现先增加后降低趋势。与土壤理化性质变化趋势类似,毛乌素沙地樟子松人工林土壤微生物生物量氮随着林龄的增加而降低,科尔沁沙地土壤微生物生物量氮随着林龄的增加而升高,呼伦贝尔沙地土壤微生物生物量氮随着林龄的增加呈先增加而后降低趋势。影响毛乌素沙地、科尔沁沙地和呼伦贝尔沙地土壤微生物生物量碳、氮的主要因子分别是硝态氮、铵态氮和有机质含量。毛乌素与科尔沁沙地樟子松人工林主要限制因子为土壤氮,而呼伦贝尔沙地樟子松受土壤有机碳限制较强。 相似文献
89.
Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery. 相似文献
90.
Zhen-Fang Yin Wen-Lu Bi Long Chen Bing Zhao Gayle M. Volk Qiao-Chun Wang 《Acta Physiologiae Plantarum》2014,36(7):1683-1692
We report a straightforward and widely applicable cryopreservation method for Lilium shoot tips. This method uses adventitious shoots that were induced from leaf segments cultured for 4 weeks on a shoot regeneration medium containing 1 mg/l α-naphthaleneacetic acid and 0.5 mg/l thidiazuron. Shoot tips (1.5–2 mm in length) including 2–3 leaf primordia were precultured on Murashige and Skoog (MS; 1962) medium with 0.5 M sucrose for 1 day and then treated with a loading solution containing 0.4 M sucrose and 2 M glycerol for 20 min, followed by a Plant Vitrification Solution 2 (PVS2) treatment for 4 h at 0 °C. Dehydrated shoot tips were transferred onto 2.5 µl PVS2 droplets on aluminum foil strips, prior to a direct immersion into liquid nitrogen for 1 h. Frozen shoot tips were re-warmed in MS medium containing 1.2 M sucrose for 20 min at room temperature, followed by post-thaw culture for shoot regrowth. Shoot regrowth levels ranged from 42.5 % for L. longiflorum × Oriental ‘Triumphator’ to 87.5 % for L. Oriental hybrid ‘Siberia’, with a mean shoot regrowth level of 67.1 % across the six diverse Lilium genotypes tested. Histological observations found that the survival patterns were similar in cryopreserved shoot tips of ‘Triumphator’ and ‘Siberia’. Assessments using inter-simple sequence repeat markers found no differences in regenerants recovered from the control stock cultures and from cryopreserved shoot tips in ‘Triumphator’ and ‘Siberia’. This Lilium droplet-vitrification cryopreservation method is efficient, simple and widely applicable for the long-term conservation of lily genetic resources. 相似文献