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| 1 | Structures of EV71 RNA-dependent RNA polymerase in complex with substrate and analogue provide a drug target against the hand-foot-and-mouth disease pandemic in China显示文摘Enterovirus 71(EV71),one of the major causative agents for hand-foot-and-mouth disease(HFMD),has caused more than 100 deaths among Chinese children since March 2008.The EV71 genome encodes an RNAdependent RNA polymerase(RdRp),denoted 3D^(pol),which is central for viral genome replication and is a key target for the discovery of specific antiviral therapeutics.Here we report the crystal structures of EV71 RdRp(3D^(pol))and in complex with substrate guanosine-5'-triphosphate and analog 5-bromouridine-5'-triphosphate best to 2.4Åresolution.The structure of EV71 RdRp(3D^(pol))has a wider open thumb domain compared with the most closely related crystal structure of poliovirus RdRp.And the EV71 RdRp(3D^(pol))complex with GTP or Br-UTP bounded shows two distinct movements of the polymerase by substrate or analogue binding.The model of the complex with the template:primer derived by superimposition with foot-and-mouth disease virus(FMDV)3D/RNA complex reveals the likely recognition and binding of template:primer RNA by the polymerase.These results together provide a molecular basis for EV71 RNA replication and reveal a potential target for anti-EV71 drug discovery. | Yang Wu Zhiyong Lou Yi Miao Yue Yu Hui Dong Wei Peng Mark Bartlam Xuemei Li Zihe Rao | 2010 | Protein & Cell2010，1，5： | 30 |
| 2 | Structure-function studies of the influenza virus RNA polymerase PA subunit显示文摘The influenza virus RNA-dependent RNA polymerase is a heterotrimeric complex (PA, PB1 and PB2) with multiple enzymatic activities for catalyzing viral RNA transcription and replication. The roles of PB1 and PB2 have been clearly defined, but PA is less well understood. The critical role of the polymerase complex in the influenza virus life cycle and high sequence conservation suggest it should be a major target for therapeutic intervention. However, until very recently, functional studies and drug discovery targeting the influenza polymerase have been hampered by the lack of three-dimensional structural information. We will review the recent progress in the structure and function of the PA subunit of influenza polymerase, and discuss prospects for the development of anti-influenza therapeutics based on available structures. | Mark BARTLAM | 2009 | Science China(Life Sciences)2009，52，5： | 8 |
| 3 | The structural basis for deadenylation by the CCR4-NOT complex显示文摘The CCR4-NOT complex is a highly conserved,multifunctional machinery controlling mRNA metabolism.Its components have been implicated in several aspects of mRNA and protein expression,including transcription initiation,elongation,mRNA degradation,ubiquitination,and protein modification.In this review,we will focus on the role of the CCR4-NOT complex in mRNA degradation.The complex contains two types of deadenylase enzymes,one belonging to the DEDD-type family and one belonging to the EEP-type family,which shorten the poly(A)tails of mRNA.We will review the present state of structure-function analyses into the CCR4-NOT deadenylases and summarize current understanding of their roles in mRNA degradation.We will also review structural and functional work on the Tob/BTG family of proteins,which are known to interact with the CCR4-NOT complex and which have been reported to suppress deadenylase activity in vitro. | Mark Bartlam Tadashi Yamamoto | 2010 | Protein & Cell2010，1，5： | 3 |
| 4 | New nsp8 isoform suggests mechanism for tuning viral RNA synthesis显示文摘During severe acute respiratory syndrome coronavirus(SARS-CoV)infection,the activity of the replication/transcription complexes(RTC)quickly peaks at 6 hours post infection(h.p.i)and then diminishes significantly in the late post-infection stages.This“down-up-down”regulation of RNA synthesis distinguishes different viral stages:primary translation,genome replication,and finally viron assembly.Regarding the nsp8 as the primase in RNA synthesis,we confirmed that the proteolysis product of the primase(nsp8)contains the globular domain(nsp8C),and indentified the resectioning site that is notably conserved in all the three groups of coronavirus.We subsequently crystallized the complex of SARS-CoV nsp8C and nsp7,and the 3-D structure of this domain revealed its capability to interfuse into the hexadecamer super-complex.This specific proteolysis may indicate one possible mechanism by which coronaviruses to switch from viral infection to genome replication and viral assembly stages. | Shuang Li Qi Zhao Yinjie Zhang Yang Zhang Mark Bartlam Xuemei Li Zihe Rao | 2010 | Protein & Cell2010，1，2： | 2 |
| 5 | Crystal Structure of Long-Chain Alkane Monooxygenase (LadA) in Complex with Coenzyme FMN: Unveiling the Long-Chain Alkane Hydroxylase显示文摘 | Liu Li Xueqian Liu Wen Yang Feng Xu Wei Wang Lu Feng Mark Bartlam Lei Wang Zihe Rao | 2007 | Journal of Molecular Biology2007，，2： | 1 |
| 6 | Structure and Cleavage Specificity of the Chymotrypsin-Like Serine Protease (3CLSP/nsp4) of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)显示文摘 | Xinsheng Tian Guangwen Lu Feng Gao Hao Peng Youjun Feng Guangpeng Ma Mark Bartlam Kegong Tian Jinghua Yan Rolf Hilgenfeld George F. Gao | 2009 | Journal of Molecular Biology2009，，4： | 1 |
| 7 | 牙龈卟啉单胞菌蛋白酶Tpr的表达、纯化和初步晶体学研究显示文摘牙龈卟啉单胞菌是一种能够引起牙周炎的口腔病原菌,能够分泌许多种蛋白酶.这些蛋白酶在获得营养、逃脱宿主免疫、粘连组织细胞和其它疾病进程中发挥了重要作用,被认为是牙周炎的重要致病因子.其中一种蛋白酶是巯基蛋白酶Tpr,它能够降解许多常见蛋白酶的底物,其活性受到营养状态和钙离子浓度的调节.本实验在大肠杆菌中表达得到Tpr蛋白,经多种方法纯化后筛选获得蛋白质晶体.通过X射线衍射实验收集到分辨率达到0.20 nm的衍射数据,并使用软件HKL2000进行了处理.这些数据为解析Tpr3维晶体结构奠定了基础. | 张琼林 Mark Bartlam | 2016 | 南开大学学报(自然科学版)2016，49，5： | 1 |
| 8 | 流感病毒聚合酶PA亚基与PB1多肽复合体的精细三维结构显示文摘近年来禽流感病毒疫情的发生给全球带来了重大威胁。对流感病毒蛋白,特别是流感病毒RNA聚合酶复合体的结构生物学研究对揭示病毒复制机制以及开展相关药物设计都具有重大意义。流感病毒RNA聚合酶是由PB1、PB2以及PA亚基组成的负责流感病毒的RNA合成以及维持病毒生命周期至关重要的分子机器。其中,PB1是该聚合酶的RNA合成亚基,PB2负责获取宿主mRNA用于病毒mRNA合成,而PA亚基功能则不清楚。本研究报道了来源于禽流感病毒RNA聚合酶PA亚基羧基端与PB1氨基端短肽复合体的三维晶体结构。该结构揭示了PA与PB1亚基相互作用方式,并分析了PA分子在RNA结合等方面的功能,对进一步研究PA功能以及开展针对聚合酶PA分子的药物设计具有十分重大的意义。 | 贺晓静 周杰 Mark Bartlam 张荣光 马建源 娄志勇 李雪梅 李晶晶 Andrzej Joachimiak 曾宗浩 葛若雯 饶子和 刘迎芳 | 2009 | 中国基础科学2009，11，2： | 1 |
| 9 | Crystal structure of human Gadd45 reveals an active dimer显示文摘The human Gadd45 protein family plays critical roles in DNA repair,negative growth control,genomic stability,cell cycle checkpoints and apoptosis.Here we report the crystal structure of human Gadd45,revealing a unique dimer formed via a bundle of four parallel helices,involving the most conserved residues among the Gadd45 isoforms.Mutational analysis of human Gadd45 identified a conserved,highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen(PCNA),p21 and cdc2,suggesting that the parallel dimer is the active form for the interaction.Cellular assays indicate that:(1)dimerization of Gadd45 is necessary for apoptosis as well as growth inhibition,and that cell growth inhibition is caused by both cell cycle arrest and apoptosis;(2)a conserved and highly acidic patch on the dimer surface,including the important residues Glu87 and Asp89,is a putative interface for binding proteins related to the cell cycle,DNA repair and apoptosis.These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function. | Wenzheng Zhang Sheng Fu Xuefeng Liu Xuelian Zhao Wenchi Zhang Wei Peng Congying Wu Yuanyuan Li Xuemei Li Mark Bartlam Zong-Hao Zeng Qimin Zhan Zihe Rao | 2011 | Protein & Cell2011，2，10： | 1 |
| 10 | 人体平衡型核苷转运蛋白的结构及应用研究进展显示文摘通过参与合成和转运核苷及其类似物,人体中的平衡型核苷转运蛋白在生物体内参与了细胞发育、能量代谢和信号转导等众多生理生化过程,其研究对于癌症、病毒感染等相关疾病的治疗有着极为重要的意义。该文综述了该类蛋白质在人体内的发现历程、分类、结构和作用机制,并对于其在一些疾病治疗和药物开发方面的前景进行了展望。 | 郝振宇 刘瑞华 王莹莹 Mark Bartlam | 2016 | 中国细胞生物学学报2016，38，6： | 1 |
| 11 | Crystallographic Studies of Cephalosporin Acylase from Pseudomonas sp. Strain 130显示文摘The cephalosporin acylases are a group of enzymes that hydrolyze cephalosporin C and/or glutaryl 7 aminocephalosporanic acid to produce 7 aminocephalosporanic acid. The cephalosporin acylase from Pseudomonas sp. strain 130 was crystallized in two different forms suitable for structural studies. A tetragonal crystal form diffracted to 0.24 nm belonged to the space group P4 12 12. There was one αβ heterodimer per asymmetric unit. A second crystal form diffracted to 0.21 nm belonged to the space group P2 1. There was four αβ heterodimers per asymmetric unit. The tetragonal crystal structure of CA 130 was determined using the multiwavelength anomalous diffraction method and the P2 1 crystal structure was then determined using the molecular replacement method. | 丁怡 姜卫红 张淑平 茅翔 Mark Bartlam 赵国平 饶子和 | 2003 | Tsinghua Science and Technology2003，8，4： | 1 |
| 12 | Crystal Structure of Methyl Parathion Hydrolase from Pseudomonas sp. WBC-3显示文摘 | Yan-Jie Dong Mark Bartlam Lei Sun Ya-Feng Zhou Zhi-Ping Zhang Cheng-Gang Zhang Zihe Rao Xian-En Zhang | 2005 | Journal of Molecular Biology2005，，3： | 1 |
| 13 | Crystal structure of human Gadd45γreveals an active dimer显示文摘Erratum to:Protein Cell 2011,2(10):814-826 DOI 10.1007/s13238-011-1090-6 Due to typesetting errors,“gadd45”should be“Gadd45γ”in the following places:the article title,the 2^(nd),4^(th) and 5^(th) Gadd45 in the ABSTRACT,the KEYWORDS,the first subti-tle of“RESULTS AND DISCUSSION”section,the legend of Figure 1,the“data collection and processing”of MATERIALS AND METHODS section. | Wenzheng Zhang Sheng Fu Xuefeng Liu Xuelian Zhao Wenchi Zhang Wei Peng Congying Wu Yuanyuan Li Xuemei Li Mark Bartlam Zong-Hao Zeng Qimin Zhan Zihe Rao | 2012 | Protein & Cell2012，3，3： | 0 |
| 14 | Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity显示文摘BTG2 is the prototypical member of the TOB family and is known to be involved in cell growth, differentiation, and DNA repair. As a transcriptional co-regulator, BTG2 | Masahiro Morita Toru Suzuki Mark Bartlam Tadashi Yamamoto | 2009 | 生物物理学报2009，25，S1： | 0 |
| 15 | 人甲状腺激素应答蛋白THRSP的晶体学研究显示文摘甲状腺激素应答蛋白THRSP(Spot14,S14)较早在研究甲状腺素在脂肪组织中的反应时被发现。该基因主要在脂肪生成组织如肝脏、脂肪和乳腺组织内表达。 | 章文正 彭伟 周卫红 曾宗浩 Mark Bartlam 饶子和 | 2009 | 生物物理学报2009，0，S1： | 0 |
| 16 | 细胞色素P450 153C1蛋白的表达、纯化及初步晶体学研究显示文摘细胞色素P450,又称CYP,是最大的酶类超家族之一,属于血红素蛋白的一个大家族[1]。它们在生物界分布极其广泛,从细菌到高等的动植物中都有分布。 | 周卫红 杨文 Stephen G.Bell Mark Bartlam Luet-Lok Wong 饶子和 | 2009 | 生物物理学报2009，0，S1： | 0 |
| 17 | Structural basis for prokaryotic calciummediated regulation by a Streptomyces coelicolor calcium binding protein显示文摘The important and diverse regulatory roles of Ca2+in eukaryotes are conveyed by the EF-hand containing calmodulin superfamily.However,the calcium-regulatory proteins in prokaryotes are still poorly understood.In this study,we report the three-dimensional structure of the calcium-binding protein from Streptomyces coelicolor,named CabD,which shares low sequence homology with other known helix-loop-helix EF-hand proteins.The CabD structure should provide insights into the biological role of the prokaryotic calcium-binding proteins.The unusual structural features of CabD compared with prokaryotic EF-hand proteins and eukaryotic sarcoplasmic calcium-binding proteins,including the bending conformation of the first C-terminalα-helix,unpaired ligand-binding EF-hands and the lack of the extreme Cterminal loop region,suggest it may have a distinct and significant function in calcium-mediated bacterial physiological processes,and provide a structural basis for potential calcium-mediated regulatory roles in prokaryotes. | Xiaoyan Zhao Hai Pang Shenglan Wang Weihong Zhou Keqian Yang Mark Bartlam | 2010 | Protein & Cell2010，1，8： | 0 |
| 18 | Structural basis for inhibition of the Tob-CNOT7 interaction by a fragment screening approach显示文摘 | Yuwei Bai (1) (2) Shinya Tashiro (3) Satoru Nagatoishi (3) Toru Suzuki (4) Dongke Yan (1) (2) Ruihua Liu (1) (2) Kouhei Tsumoto (3) Mark Bartlam (1) (2) Tadashi Yamamoto (4) | 2015 | Protein & Cell2015，6，12： | 0 |
| 19 | 人抗增殖蛋白Tob与其配体蛋白的相互作用及功能研究显示文摘抗增殖蛋白Tob作为BTG/TOB家族成员之一,对细胞增殖与mRNA降解具有重要作用.在磷酸激酶Erk1和Erk2的作用下,Tob中的3个丝氨酸位点可以进行磷酸化.已有大量研究表明Tob通过与去腺苷酸化酶中的核糖核酸酶D家族成员之一的Caf1相互作用于mRNA 3′端,共同组成去腺苷酸化酶复合体.同时,Tob对胞质多聚腺苷酸化因子结合蛋白3(CPEB3)对蛋白表达的负调控具有抑制作用.并且,Tob可以与多聚腺苷酸结合蛋白(PABP)相互作用,促进细胞内mRNA脱腺苷化.通过对Tob的3个参与磷酸化的丝氨酸位点进行突变,分别研究了人源野生型与丝氨酸突变型Tob对其与人源Caf1,PABP及CPEB3相互作用及多聚腺苷酸降解过程的影响. | 白玉巍 张琼林 Mark Bartlam | 2015 | 南开大学学报(自然科学版)2015，48，3： | 0 |
| 20 | A novel non-radioactive assay for HIV-RT(RdDp)based on pyrosequencing for high-throughput drug screening显示文摘Current in vitro assays for the activity of HIV-RT(reverse transcriptase)require radio-labeled or chemically modified nucleotides to detect reaction products.However,these assays are inherently end-point measurements and labor intensive.Here we describe a novel non-radioactive assay based on the principle of pyrosequencing coupledenzyme system to monitor the activity of HIV-RT by indirectly measuring the release of pyrophosphate(PPi),which is generated during nascent strand synthesis.The results show that our assay could monitor HIV-RT activity with high sensitivity and is suitable for rapid highthroughput drug screening targeting anti-HIV therapies due to its high speed and convenience.Moreover,this assay can be used to measure primase activity in an easy and sensitive manner,which suggests that this novel approach could be wildly used to analyze the activity of PPi-generated and ATP-free enzyme reactions. | Chang Zhang Yang Wu Yuna Sun Chuan Hong Kehui Xiang Yu Guo Mark Bartlam Zhiyong Lou | 2010 | Protein & Cell2010，1，3： | 0 |
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