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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 | Infertility counseling: the issue experience of setting upatelephone counseling service 显示文摘 | Bernadette Bartlam John Mcleod | 2000 | Patient Education and Counseling2000，41，： | 1 |
| 7 | Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus显示文摘 | He Xiaojing Zhou Jie Bartlam M | 2008 | Nac Lett2008，454，： | 1 |
| 8 | Crystal structure of an avian influenza polymerase PAN reveals an endonuclease active site 显示文摘 | Yuan P Bartlam M Lou Z | 2009 | Nature2009，458，7240： | 1 |
| 9 | Crystal structure of the polymerase PA ( C ) -PB1 ( N ) complex from an avian influenza H5N1 virus显示文摘 | He X Zhou J Bartlam M | 2008 | Nature2008，454，7208： | 1 |
| 10 | Purification, crystallization and X- ray analysis of swine vesicular disease virus显示文摘 | IAn W Zhao Q Bartlam M | 2002 | Acta Crystallogr D Biol Crystallogr2002，，58： | 1 |
| 11 | Crystal structure of an avian influenza polymerase PANreveals an endonuclease active site显示文摘 | Yuan P Bartlam M Lou Z | 2009 | Nature2009，458，7240： | 1 |
| 12 | WONCA研究论文摘要汇编——全科医生和患者对分层护理的看法:理论获知调查显示文摘背景分层护理包括改变全科医生治疗患者的临床表现,脱离当前的阶梯式治疗方法,以确定早期治疗方案作为替代,从而与患者持续的致残性疼痛的风险相匹配。本文探讨了英国全科医生和患者对预后分层护理模式的看法,针对患有5种基层医疗最常见的肌肉骨骼疼痛表现的患者正在开发该模式。重点是日常实践中使用分层护理的可接受性,预期的障碍和促进因素。方法全科医生(n=23)组成四个焦点小组进行六个半结构化的电话采访,患者(n=20)组成三个焦点小组。主题性分析数据并确定检查过的与理论域框架(TDF)相关的主题,这有利于综合鉴定行为改变的决定因素。TDF中采取批评方法,检验理论域之间具有细微差别的相互关系。结果本文辨认出4个关键性主题:由分层护理指导的临床决策的可接受性;治疗关系的影响;生物医学模式中植入预后方法;使用分层护理的实际问题。报道每个主题内的特定研究发现,主题间共性是理论域之间的关系,即已确定的知识、技能、职业角色和身份,环境背景和资源,以及目标之间的关联。通过分析已确定的关系,本文如果全科医生和患者认为分层护理是可接受的,那么其必须被视为能够提高全科医生的知识和技能,而非削弱全科医生和患者各自的身份,并且与最小破坏的咨询环境背景相整合。结论研究结果强调在干预时考虑全科医学情境的重要性,支持全科医生针对临床表现做出改变。调查结果将告知研究项目的进一步阶段;具体而言,即全科医生参与将来的随机对照试验(RCT)的干预形式和支持包内容。该研究同时对理论争论做出了贡献,即如何最好地鼓励全科医生在全科医学中改变其临床行为和在这一过程中TDF可能发挥的作用。 | SAUNDERS B BARTLAM B FOSTER N E 本刊编辑部 | 2016 | 中国全科医学2016，19，29： | 1 |
| 13 | Crystal structure of the pyridoxal- 5' -phosphate -dependent serine dehydratase from human liver显示文摘 | Sun L Bartlam M Liu Y | 2005 | Protein Sci2005，14，3： | 1 |
| 14 | Crystal structure of the polymerase PAC-PB1Ncomplex from an avian influenza H5N1 virus显示文摘 | He X Zhou J Bartlam M | 2008 | Nature2008，454，7208： | 1 |
| 15 | Crystal structure of the polymerase PA(C)-PB1(N)complex from an avian influenza H5N1virus显示文摘 | He X Zhou J Bartlam M Zhang R Ma J Lou Z Li X Li J Joachimiak A Zeng Z Ge R Rao Z Liu Y | 2008 | Nature2008，454，7208： | 1 |
| 16 | Crystal structure of an avian influenza polymerase PA(N)reveals an endonuclease active site显示文摘 | Yuan P Bartlam M Lou Z Chen S Zhou J He X Lv Z Ge R Li X Deng T Fodor E Rao Z Liu Y | 2009 | Nature2009，458，7240： | 1 |
| 17 | Crystal structure of an acylpeptide hydrolase/esterase from seropyrum pemix K1 显示文摘 | Bartlam M | 2004 | Structure2004，12，8： | 1 |
| 18 | Structure-function studies of the influenza vires RNA polymerase PA subunit 显示文摘 | Liu YF Lou ZY Bartlam M | 2009 | Science in China series C: Life science2009，52，5： | 1 |
| 19 | Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation显示文摘 | He H Ding Y Bartlam M Sun F Le Y Qin X | 2003 | J Mol Biol2003，325，5： | 1 |
| 20 | Crystal structure of anavian influenza polymerase PAN reveals an endonucleaseactive site显示文摘 | Yuan P Bartlam M Lou Z | 2009 | Nature2009，458，7240： | 1 |
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