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| 1 | A complete sequence and comparative analysis of a SARS-associated virus(Isolate BJ01)显示文摘The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs. We report the complete genome sequence and comparative analysis of an isolate (BJ01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS- associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymous mutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to beinvolved in the immunoreactions between the virus and its host. Two amino acid changes have been detected in the Mprotein, which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides noevidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of otherpossible SARS-related pathogen(s). | QIN E'de ZHU Qingyu YU Man FAN Baochang CHANG Guohui SI Bingyin YANG Bao PENG Wenming JIANG Tao LIU Bohua DENG Yongqiang LIU Hong ZHANG Yu WANG Cui LI Yuquan GAN Yonghua LI Xiaoyu L Fushuang TAN Gang CAO Wuchun, YANG Ruifu Institute of Microbiology and Epidemiology, Chinese Academy of Military Medical Sciences, Beijing 100071, China WANG Jian, LI Wei, XU Zuyuan, LI Yan, WU Qingfa, LIN Wei, CHEN Weijun, TANG Lin, DENG Yajun, HAN Yujun, LI Changfeng, LEI Meng, LI Guoqing, LI Wenjie, L Hong, SHI Jianping, TONG Zongzhong, ZHANG Feng, LI Songgang, LIU Bin, LIU Siqi, DONG Wei, WANG Jun, Gane K-S Wong, YU Jun & YANG Huanming* Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300 National Center for Genome Information, Beijing 101300, China | 2003 | Chinese Science Bulletin2003，48，10： | 121 |
| 2 | 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers显示文摘象 5-methylcytosine (5mC ) 和 5-hydroxymethylcytosine (5hmC ) 那样的 DNA 修正是知道在哺乳动物影响全球基因表示的 epigenetic 标记。在人的染色体,与基因表示的靠近的关联和高化学的稳定性给他们的流行,这些 DNA epigenetic 标记能为癌症用作理想的 biomarkers 诊断。利用一种高度敏感、选择的化学标记技术,我们这里报导在传播没有房间的 DNA ( cfDNA )并且在从最近与 colorectal 诊断的 260 个病人的一个队收集的配对的肿瘤和邻近的纸巾的 genomic DNA ( gDNA )的 5hmC 的染色体宽的介绍,胃,胰腺,从 90 个健康个人的肝或甲状腺癌症和正常纸巾。5hmC 主要在与开的染色质和容许的 histone 修正重合的 transcriptionally 活跃的区域被散布。柔韧的联系癌症的 5hmC 签名在 cfDNA 被识别为特定的癌症类型是特征的。传播 cfDNA 的 5hmC 底 biomarkers colorectal 和胃的癌症是高度预兆的并且比常规 biomarkers 优异并且比得上从织物活体检视的 5hmC biomarkers。因此,这新策略能从血样品的分析为癌症的诊断和预后导致有效、最低限度地侵略的方法的发展。 | Wenshuai Li Xu Zhang Xingyu Lu Lei You Yanqun Song Zhongguang Luo Jun Zhang Ji Nie Wanwei Zheng Diannan Xu Yaping Wang Yuanqiang Dong Shulin Yu Jun Hong Jianping Shi Hankun Hao Fen Luo Luchun Hua Peng Wang Xiaoping Qian Fang Yuan Lianhuan Wei Ming Cui Taiping Zhang Quan Liao Menghua Dai Ziwen Liu Ge Chen Katherine Meckel Sarbani Adhikari Guifang Jia Marc B Bissonnette Xinxiang Zhang Yupei Zhao Wei Zhang Chuan He Jie Liu | 2017 | Cell Research2017，27，10： | 30 |
| 3 | Fundamental geological elements for the occurrence of Chinese marine oil and gas accumulations显示文摘The Paleozoic strata in the Tarim Basin, Sichuan Basin and Ordos Basin are the major targets for marine petroleum exploration, with developed high quality hydrocarbon, mainly argillite. The deep burial of these source rocks suggests that they mainly develop gas instead of oil. But different maturities of organic matter may lead to different hydrocarbon facies. Through thermochemical sulfate reduction (TSR), the hydrocarbon in the carbonate rocks may undergo a process of pyrolytic cracking and be catalyzed into gases. The marine reservoirs mainly consist of carbonate and clastic rocks, and the former is controlled by sedimentary facies, dolomitization, solution, TSR and cracking. The multiphase tectonic cycling develops multiple source-reservoir-cap combinations and diversified types of traps and reservoirs, featuring multiphase reservoir formation, mainly late-phase formation or consolidation. Palaeo-uplifts play a controlling role in hydrocarbon accumulation. Differences in major source rocks in the three basins lead to different locations of oil-gas accumulation layers, different types and patterns of reservoirs and different features of reservoir formation. | ZHANG ShuiChang LIANG DiGang ZHU GuangYou ZHANG XingYang ZHANG BaoMin CHEN JianPing ZHANG Bin | 2007 | Chinese Science Bulletin2007，52，A01： | 22 |
| 4 | Adapting liposomes for oral drug delivery显示文摘Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes,oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract,difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes. | Haisheng He Yi Lu Jianping Qi Quangang Zhu Zhongjian Chen Wei Wu | 2019 | Acta Pharmaceutica Sinica B2019，9，1： | 23 |
| 5 | A review of ecological restoration techniques in fluvial rivers显示文摘Rivers play an important role in people's living and agricultural production,however,intense human activities have broken the original ecological balance,and affected structures and functions of the river ecosystem.To restore the damaged river ecosystem back to a healthy status,effective ecological restoration measures need to be implemented.The main problems that the damaged rivers face are either the locally altered hydrological processes affected by construction of hydraulic facilities,or the deterioration of water quality resulted from pollution emissions,or both.In this study,ecological restoration techniques of the rivers affected by engineering control or pollution are reviewed respectively.In addition,three kinds of methods,i.e.physical,chemical and biological-ecological methods are introduced in details for the rivers affected by water pollution.At present,the development of river restoration techniques shows the following trends:1) the scale of ecological restoration is becoming larger;2) ecological restoration measures are required to meet multiple objectives;and 3) the management of water environment is changing from water quality management to aquatic ecosystem management. | Baozhu Pan Jianping Yuan Xinhua Zhang Zhaoyin Wang Jiao Chen Jinyou Lu Wenjun Yang Zhiwei Li Na Zhao Mengzhen Xu | 2016 | International Journal of Sediment Research2016，31，2： | 18 |
| 6 | Eco-environment range in the source regions of the Yangtze and Yellow rivers显示文摘Based on geographical and hydrological extents delimited, four principles are identified, as the bases for delineating the ranges of the source regions of the Yangtze and Yellow rivers in the paper. According to the comprehensive analysis of topographical characteristics, climate conditions, vegetation distribution and hydrological features, the source region ranges for eco-environmental study are defined. The eastern boundary point is Dari hydrological station in the upper reach of the Yellow River. The watershed above Dari hydrological station is the source region of the Yellow River which drains an area of 4.49×10 4 km 2 . Natural environment is characterized by the major topographical types of plateau lakes and marshland, gentle landforms, alpine cold semi-arid climate, and steppe and meadow vegetation in the source region of the Yellow River. The eastern boundary point is the convergent site of the Nieqiaqu and the Tongtian River in the upstream of the Yangtze River. The watershed above the convergent site is the source region of the Yangtze River, with a watershed area of 12.24×10 4 km 2 . Hills and alpine plain topography, gentle terrain, alpine cold arid and semi-arid climate, and alpine cold grassland and meadow are natural conditions in the source region of the Yangtze River. | DING Yongjian,YANG Jianping,LIU Shiyin,CHEN Rensheng,WANG Genxu,SHEN Yongping,WANG Jian,XIE Changwei,ZHANG Shiqing(Cold and Arid Regions Environmental and Engineering Research Institute, CAS, Lanzhou 730000, China) | 2003 | Journal of Geographical Sciences2003，13，2： | 18 |
| 7 | Safety issues and new rapid detection methods in traditional Chinese medicinal materials显示文摘The safety of traditional Chinese medicine(TCM) is a major strategic issue that involves human health. With the continuous improvement in disease prevention and treatment, the export of TCM and its related products has increased dramatically in China. However, the frequent safety issues of Chinese medicine have become the ‘bottleneck' impeding the modernization of TCM. It was proved that mycotoxins seriously affect TCM safety; the pesticide residues of TCM are a key problem in TCM international trade; adulterants have also been detected, which is related to market circulation. These three factors have greatly affected TCM safety. In this study, fast, highly effective, economically-feasible and accurate detection methods concerning TCM safety issues were reviewed, especially on the authenticity, mycotoxins and pesticide residues of medicinal materials. | Lili Wang Weijun Kong Meihua Yang Jianping Han Shilin Chen | 2015 | Acta Pharmaceutica Sinica B2015，5，1： | 18 |
| 8 | Gastrodin prevents steroid-induced osteonecrosis of the femoral head in rats by anti-apoptosis显示文摘 | Zheng Huifeng Yang Erping Peng Hao Li Jianping Chen Sen Zhou Jianlin Fang Hongsong Qiu Bo Wang Zhe | 2014 | Chinese Medical Journal2014，，22： | 17 |
| 9 | QUADRATIC OPTIMIZATION METHOD AND ITS APPLICATION ON OPTIMIZING MECHANISM PARAMETER显示文摘以便设计的机制与最佳的动力学行为满足 kinematics 的要求,一个二次的优化方法基于运动学、动态的优化的不同特征被建议。这个方法包括优化的二步,也就是说运动学、动态的优化。同时,它把运动学的优化的结果用作动态优化的限制方程。这个方法在与显著意义与 high-speedrice 幼苗 transplanter 的椭圆形的行星的齿轮移植机制的参数优化被使用。参数光谱,相遇到运动学的要求,在 kinematics 优化通过设想的人机相互作用被获得,并且最佳的参数在动态优化基于改进基因算法被获得。在动态优化,客观功能作为 theoptimal1 被选动态行为,限制方程从运动学的优化的结果。当两个都运动学、动态的表演充当客观功能时,这个方法对多客观的优化合适。 | ZHAO Yun CHEN Jianneng YU Yaxin YU Gaohong ZHU Jianping | 2006 | Chinese Journal of Mechanical Engineering2006，19，4： | 14 |
| 10 | 3D Positional and Quantitative Prediction of the Xiaoqinling Gold Ore Belt in Tongguan, Shaanxi, China显示文摘Quantitative prediction of deep orebody based on 3D visualization technology is of great significance in mineral exploration. Based on the 2D traditional quantitative predicting method, the geoanomaly theory and the mineral exploration model idea, we constructed 3D models of the topography, strata, structure, magmatite and prospecting engineering of the study area using the commercial 3D modeling software Micromine, delineated eight prospective areas and estimated the gold resources amount with methods of Abundance Estimation and Volume Estimation. Then, we compared and counted the known ore blocks and the predicted blocks, which quantitatively explains this prediction's validity. The results show that Xiaoqinling gold belt in Tongguan has convincing potential for gold development and utilization and the prediction method based on 3D visualization technology proves to be effective. | CHEN Jianping SHI Rui CHEN Zhenping WANG Limei SUN Yan | 2012 | Acta Geologica Sinica(English Edition)2012，86，3： | 14 |
| 11 | Comparison of dust emissions, transport, and deposition between the Taklimakan Desert and Gobi Desert from 2007 to 2011显示文摘The Taklimakan Desert(TD) and Gobi Desert(GD) are two of the most important dust sources in East Asia, and have important impact on energy budgets, ecosystems and water cycles at regional and even global scales. To investigate the contribution of the TD and the GD to dust concentrations in East Asia as a whole, dust emissions, transport, and deposition over the TD and the GD in different seasons from 2007 to 2011 were systematically compared, based on the Weather Research and Forecasting model coupled with Chemistry(WRF-Chem). Dust emissions, uplift, and long-range transport related to these two dust source regions were markedly different due to differences in topography, elevation, thermal conditions, and atmospheric circulation. Specifically,the topography of the GD is relatively flat, and at a high elevation, and the area is under the influence of two jet streams at high altitudes, resulting in high wind speeds in the upper atmosphere. Deep convective mixing enables the descending branch of jet streams to continuously transport momentum downward to the mid-troposphere, leading to enhanced wind speeds in the lower troposphere over the GD which favors the vertical uplift of the GD dust particles. Therefore, the GD dust was very likely to be transported under the effect of strong westerly jets, and thus played the most important role in contributing to dust concentrations in East Asia. Approximately 35% and 31% of dust emitted from the GD transported to remote areas in East Asia in spring and summer, respectively. The TD has the highest dust emission capabilities in East Asia, with emissions of about 70.54 Tg yr.1 in spring, accounting for 42% of the total dust emissions in East Asia. However, the TD is located in the Tarim Basin and surrounded by mountains on three sides. Furthermore, the dominant surface wind direction is eastward and the average wind speed at high altitudes is relatively small over the TD. As a result, the TD dust particles are not easily transported outside the Tarim Basin, such that most of the dust particles are re-deposited after uplift, at a total deposition rate of about 40 g m.2. It is only when the TD dust particles are uplifted above 4 km, and entrained in westerlies that they begin to undergo a long-range transport. Therefore,the contribution of the TD dust to East Asian dust concentrations was relatively small. Only 25% and 23% of the TD dust was transported to remote areas over East Asia in spring and summer, respectively. | CHEN SiYu HUANG JianPing LI JingXin JIA Rui JIANG NanXuan KANG LiTai MA XiaoJun XIE TingTing | 2017 | Science China Earth Sciences2017，60，7： | 14 |
| 12 | Recent progress towards mild-condition ammonia synthesis显示文摘Ammonia is essential for food and energy.Industrial ammonia synthesis via Haber–Bosch process is energy-intensive and releases large amount of CO2.Increasing research efforts are devoted to 'green'ammonia synthesis.The present article reviews the recent progress in the fields of thermocatalytic, electrocatalytic, photocatalytic and chemical looping processes for dinitrogen reduction towards ammonia formation and discusses the challenges borne for mild-condition synthesis. | Qianru Wang Jianping Guo Ping Chen | 2019 | Journal of Energy Chemistry2019，28，9： | 13 |
| 13 | RS and GIS-based Statistical Analysis of Secondary Geological Disasters after the 2008 Wenchuan Earthquake显示文摘用 RS 和 GIS 工具,这篇文章在 Wenchuan 县,四川省,中华人民共和国以及大规模山崩的特征分析一般地质的特征和结构的带分发特征,泥岩石流动,地震湖,等等,在地震以后在 2008 年 5 月 12 日。基于上述工作,全面室内、室外的研究在有地震,地面,阶层,岩性学,和结构的灾难分发特征和他们的关系上被发射。证据方法的重量被利用到份量上分析并且在地震发生了以后,评估第二等的地质的灾难的空间分发。为第二等的地质的灾难的 3 补救等级从证据的重量的结果被导出,由给补救地震的建议列在后面第二等的灾难。 | CHEN Jianping LI Jianfeng QIN Xuwen DONG Qingji SUN Yan | 2009 | Acta Geologica Sinica(English Edition)2009，83，4： | 13 |
| 14 | 2018 update of expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI显示文摘East Asians are the most populous race in the world and their health status is an important global issue.Compared with Caucasian populations, East Asian patients have a different benefit/risk ratio when using antithrombotic treatment. Despite this observation, treatment strategies in East Asian patients are mostly based on the American and European guidelines. Despite a lower platelet inhibitory response to clopidogrel, East Asian patients show a similar or even a lower rate of ischemic event occurrence and higher bleeding risk compared with Caucasian patients. For potent P2Y_(12) inhibitors(ticagrelor and prasugrel),East Asian patients have shown less favorable net clinical benefits compared with Caucasian patients,which may be related to differences in pharmacokinetic/pharmacodynamic profiles and therapeutic zone of antiplatelet effect. This updated consensus mainly focuses on state-of-the-art and current controversies in the East Asian population. In addition, when East Asian patients are administered potent P2Y_(12) receptor inhibitors, the strategies and ongoing trials to overcome the related hurdles are discussed. | Yong Huo Young-Hoon Jeong Yanjun Gong Daowen Wang Ben He Jiyan Chen Guosheng Fu Yundai Chen Jianping Li Yi Li Shinya Goto Udaya S.Tantry Paul A.Gurbel Jong-Hwa Ahn Hyo-Soo Kim Myung Ho Jeong Yaling Han Sidney C.Smith Jr. Junbo Ge | 2019 | Science Bulletin2019，64，3： | 12 |
| 15 | Comparative analysis of astaxanthin and its esters in the mutant E1 of Haematococcus pluvialis and other green algae by HPLC with a C30 column显示文摘A gradient reversed-phase high-performance liquid chromatography (HPLC) method using a C30 col-umn was developed for the simultaneous determination of astaxanthin, astaxanthin monoesters and astaxanthin diesters in the green algae Chlorococcum sp., Chlorella zofingiensis, Haematococcus plu-vialis and the mutant E1, which was obtained from the mutagenesis of H. pluvialis by exposure to UV-irradiation and ethyl methanesulphonate (EMS) with subsequent screening using nicotine. The re-sults showed that the contents of total astaxanthins including free astaxanthin and astaxanthin esters ranged from 1.4 to 30.9 mg/g dry biomass in these green algae. The lower total astaxanthin levels (< 2 mg/g dry biomass) were detected in the green algae Chlorococcum sp. and C. zofingiensis. The higher total astaxanthin levels (>16 mg/g dry biomass) were found in the green alga H. pluvialis and its mutant E1. It is notable that the mutant E1 is found to have considerably higher amounts of total astaxanthin (30.9 mg/g) as compared to the wild strain of H. pluvialis (16.1 mg/g). This indicates that UV-irradiation and EMS compound mutagenesis with subsequent screening using nicotine is an effective method for breeding of a high-producing astaxanthin strain of H. pluvialis. In addition, the green alga C. zofingien-sis had a remarkably higher percentage of astaxanthin diesters (76.3% of total astaxanthins) and a re-markably lower percentage of astaxanthin monoesters (18.0% of total astaxanthins) in comparison with H. pluvialis (35.5% for diesters and 60.9% for monoesters), the mutant E1 (49.1% and 48.1%) and Chlorococcum sp. (18.0% and 58.6%). | PENG Juan1, XIANG WenZhou2,1, TANG QuanMing1, SUN Ni1, CHEN Feng1,3 & YUAN JianPing 4 1 South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China 2 Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China 3 School of Biological Sciences, The University of Hong Kong, Hong Kong, China 4 Institute of Oceanology & College of Life Sciences, Sun Yat-Sen University, Guangzhou 510301, China | 2008 | Science China(Life Sciences)2008，51，12： | 12 |
| 16 | A discussion on gas sources of the Feixianguan Formation H_2S-rich giant gas fields in the northeastern Sichuan Basin显示文摘In recent years several H2S-rich oolite giant gas pools have been discovered in the Lower Triassic Feixianguan Formation of the northeastern Sichuan basin, and their explored gas reserves have been over 5000×108 m3. However, gas sources remain unsolved due to multiple source horizons with high maturity in this area and TSR alterations. By integrating analytical data of natural gas samples with conprehensive investigations on many factors, such as oil-gas geology, distribution and evolution of source rocks, charging and adjustment of gas pools, mixture of natural gases and secondery alterations, the present study concluded that the dominant source for the Feixianguan Fr. gas pools is the Permian Longtan Fr. source rock and secondly the Silurian Longmaxi Fr. source rock. Natural gases from the various gas pools differ genetically due to the matching diversity of seal configurations with phases of hydrocarbon generation and expulsion by different source rocks, among which natural gases in Puguang Gasfield are dominated by the trapped gas generated from the Longtan Fr. source rock and commingled with the gas cracked from the Silurian crude oil, while those in Dukouhe, Tieshangpo and Luojiazhai Gasfields are composed mainly of the Silurian oil-cracking gas and commingled with the natural gas derived from the Longtan Fr. source rock. | ZHANG ShuiChang ZHU GuangYou CHEN JianPing LIANG YingBo | 2007 | Chinese Science Bulletin2007，52，A01： | 12 |
| 17 | H. pylori Escape Host Immunoreaction Through Inhibiting ILK Expression by VacA显示文摘Helicobacter pylori (H。pylori ) 尽管有精力旺盛的有免疫力的回答,固执地开拓殖民地于胃的 mucosa。Vacuolating 细胞毒素由 H 藏匿了。pylori 结果是有势力 immunomodulatory 毒素,而是包含的信号 transduction 小径没在巨噬细胞被学习。我们在这研究观察了那 vacA 缺乏的 H。pylori 导致了连接 integrin 的 kinase (同类) 和 endothelial 的显著地更高的表示氮的氧 synthase (eNOS ) ,并且显著地在 monocyte/macrophage-like U937 房间的反应的氧种类(ROS ) 的更多的生产,同样与 isogenic vacA+H 相比。pylori。在 U937 房间 overexpressing 同类的 eNOS mRNA 的表示显著地与空向量与那些 transfected 相比被增加。因此, vacA 缺乏的 H。pylori 出现到 upregulate 同类表示,调制 eNOS 并且作为结果的表示,刺激 ROS 的生产。,帮助 H 是 VacA 由禁止同类表示阻止如此的进程。pylori 逃跑主人免疫反应。这机制解释,至少部分地, H 的坚持的感染。在胃的 pylori。 | Jianping Yuan Ping Li Jing Tao Xiaodong Shi Baoyu Hu Huabiao Chen Xiaokui Guo | 2009 | Cellular & Molecular Immunology2009，6，3： | 12 |
| 18 | A Dormant Multi-Controller Model for Software Defined Networking显示文摘In order to improve the scalability and reliability of Software Defined Networking(SDN),many studies use multiple controllers to constitute logically centralized control plane to provide load balancing and fail over.In this paper,we develop a flexible dormant multi-controller model based on the centralized multi-controller architecture.The dormant multi-controller model allows part of controllers to enter the dormant state under light traffic condition for saving system cost.Meanwhile,through queueing analysis,various performance measures of the system can be obtained.Moreover,we analyze the real traffic of China Education Network and use the results as the parameters of computer simulation and verify the effects of parameters on the system characteristics.Finally,a total expected cost function is established,and genetic algorithm is employed to find the optimal values of various parameters to minimize system cost for the deployment decision making. | FU Yonghong BI Jun WU Jianping CHEN Ze WANG Ke LUO Min | 2014 | China Communications2014，11，3： | 11 |
| 19 | In vitro and in vivo antibacterial activity of Pogostone显示文摘 | Peng Fu Wan Feng Xiong Liang Peng Cheng Dai Min Chen Jianping | 2014 | Chinese Medical Journal2014，，23： | 11 |
| 20 | Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H显示文摘人的 cytosolic NADP-IDH (IDH1 ) 最近被发现了涉及 tumorigenesis。尤其是,到目前为止识别的导出肿瘤的 IDH1 变化主要发生在 Arg132,和变化 R132H 是最流行的。这个变化损害酶的氧化 IDH 活动,但是显示把伪 - ketoglutarate (伪 K G ) 变换成 2-hydroxyglutarate 的新减小功能。这里,我们报导有或没有 isocitrate (ICT ) 的 R132H 变异的 IDH1 的结构跳了。和 mutagenesis 的结构的数据和生物化学的数据揭示一个以前未定义的起始的 ICT 有约束力的状态并且证明那项 IDH 活动要求一个 conformational 变化到一关门预先转移状态。Arg132 在催化反应起多重功能的作用;特别地, R132H 变化从起始的 ICT 有约束力的状态妨碍 conformational 变化到预先转移状态,导致 IDH 活动的缺陷。我们的结果第一次描述那有中间的符合构造,对应于一个起始的 ICT 有约束力的状态并且 R132H 变化能在这符合构造套住酶,因此使潜在地肿瘤镇压的 IDH 活动的鈥渙f f 开关鈥 ? 的分子的机制清楚些。而且,我们为获得的 伪K G 减小活动证明了 Tyr139 的必要性并且建议 Tyr139 可以由从 NADPH 在一个氢化物阴离子的转移期间在 伪K G 的 C2 原子上补偿增加的否定费用到 伪K G 起一个重要作用,它提供新卓见进 鈥渙n 开关鈥?的机制假设地由这个变化的 IDH1 的 oncogenic 减小活动。 | Bei Yang Chen Zhong Yingjie Peng Zheng Lai Jianping Ding | 2010 | Cell Research2010，20，11： | 11 |
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