生物化学简介--课件

生物化学生物化学BiochemistryBiochemistry1ppt课件绪论绪论大纲：课程主要内容及要求大纲：课程主要内容及要求引子：生物化学的历史和发展趋势引子：生物化学的历史和发展趋势2ppt课件教材：教材：生物化学生物化学，第三版，王镜岩等主编，第三版，王镜岩等主编，20022002年，高教出版社年，高教出版社参考书：参考书：1.Biochemistry,1.Biochemistry,Jeremy M.Berg,John L.Tymoczko,Lubert Jeremy M.Berg,John L.Tymoczko,Lubert StryerStryer 5th edition W.H.Freeman and Company 5th edition W.H.Freeman and Company2.Biochemistry,Donald Voet,Judith G.Voet2.Biochemistry,Donald Voet,Judith G.Voet.3 3rdrd edition,2003,John Wiley&Sons,Inc.edition,2003,John Wiley&Sons,Inc.New York.New York.3ppt课件生物化学（上）生物化学（上）6060学时学时其中上课时间：其中上课时间：5454学时学时4ppt课件第一章第一章 绪论绪论 (3(3学时学时)（周丛照）（周丛照）第二章第二章 蛋白质蛋白质 (15(15学时学时)（周丛照）（周丛照）2.1 202.1 20种氨基酸的结构和性质（种氨基酸的结构和性质（2 2学时）学时）2.2 2.2 蛋白质中的二级结构（蛋白质中的二级结构（1 1学时）学时）2.3 2.3 蛋白质的高级结构（蛋白质的高级结构（3 3学时）学时）2.4 2.4 血红蛋白和免疫球蛋白的结构与功能（血红蛋白和免疫球蛋白的结构与功能（3 3学时）学时）2.5 2.5 维持蛋白质高级结构的作用力（维持蛋白质高级结构的作用力（1 1学时）学时）2.6 2.6 蛋白质折叠和结构进化蛋白质折叠和结构进化 （2 2学时）学时）2.7 2.7 蛋白质分离纯化（蛋白质分离纯化（3 3学时）学时）第三章第三章 核酸（核酸（6 6学时学时)3.13.1核酸和核苷酸的结构、性质和功能核酸和核苷酸的结构、性质和功能 （3 3学时）学时）3.2 3.2 核酸的研究方法核酸的研究方法 （3 3学时）学时）5ppt课件第四章糖（第四章糖（3 3学时）学时）4.14.1糖的生物学作用（糖的生物学作用（1 1学时）学时）4.24.2单糖和多糖（单糖和多糖（1 1学时）学时）4.34.3糖蛋白（糖蛋白（1 1学时）学时）第五章第五章 脂类和生物膜（脂类和生物膜（6 6学时）学时）5.15.1脂的分类和性质（脂的分类和性质（3 3学时）学时）5.25.2生物膜（生物膜（2 2学时）学时）5.35.3膜蛋白（膜蛋白（1 1学时）学时）6ppt课件第六章第六章 酶（酶（1515学时）学时）6.16.1酶的发展历史、作用特征及催化机理酶的发展历史、作用特征及催化机理(3(3学时学时)6.26.2酶的分类及酶功能的多样性（酶的分类及酶功能的多样性（2 2学时）学时）6.36.3核酶（核酶（1 1学时）学时）6.46.4酶促反应动力学（酶促反应动力学（3 3学时）学时）6.5 6.5 酶的抑制作用（酶的抑制作用（3 3学时）学时）6.66.6别构酶及其作用原理（别构酶及其作用原理（3 3学时）学时）第七章第七章 维生素与激素（维生素与激素（6 6学时）学时）（周丛照）（周丛照）7.17.1维生素与辅酶（维生素与辅酶（3 3学时）学时）7.27.2激素及其作用原理（激素及其作用原理（3 3学时）学时）7ppt课件生物化学（下）生物化学（下）4040学时学时其中上课时间其中上课时间 3636学时学时8ppt课件第八章第八章 代谢总论（代谢总论（3 3学时）学时）8.18.1代谢及代谢途径的相关概念（代谢及代谢途径的相关概念（1 1学时）学时）8.1 8.1 生物能学（生物能学（2 2学时）学时）第九章第九章 生物膜和物质运输（生物膜和物质运输（3 3学时）学时）9.19.1物质跨膜运输的方式物质跨膜运输的方式 （0.50.5学时）学时）9.29.2小分子物质的运输（小分子物质的运输（1 1学时）学时）9.39.3离子载体（离子载体（1 1学时）学时）9.49.4生物大分子的跨膜运输（生物大分子的跨膜运输（0.50.5学时）学时）第十章第十章 糖酵解（糖酵解（6 6学时）学时）10.110.1糖酵解概述（糖酵解概述（1 1学时）学时）10.210.2糖酵解的第一阶段（糖酵解的第一阶段（2 2学时）学时）10.310.3糖酵解的第二阶段（糖酵解的第二阶段（2 2学时）学时）10.410.4糖酵解的调控（糖酵解的调控（1 1学时）学时）9ppt课件第十一章第十一章 柠檬酸循环柠檬酸循环 （3 3学时）学时）11.111.1柠檬酸循环的准备阶段柠檬酸循环的准备阶段 （0.50.5学时）学时）11.211.2柠檬酸循环的反应机制柠檬酸循环的反应机制 （2 2学时）学时）11.311.3柠檬酸循环的调控柠檬酸循环的调控 （0.50.5学时）学时）第十二章第十二章 生物氧化（生物氧化（6 6学时）学时）12.112.1生物氧化基本概念和呼吸链（生物氧化基本概念和呼吸链（1.51.5学时）学时）12.212.2氧化还原电位和自由能变化（氧化还原电位和自由能变化（0.50.5学时）学时）12.212.2氧化磷酸化（氧化磷酸化（4 4学时）学时）第十三章第十三章 光合作用（光合作用（3 3学时）学时）13.113.1光合作用概况（光合作用概况（1 1学时）学时）13.213.2光合磷酸化和光合磷酸化和CO2CO2固定（固定（2 2学时）学时）10ppt课件第十四章第十四章 糖原的分解和生物合成糖原的分解和生物合成 （3 3学时）学时）14.114.1糖原的降解和糖原的生物合成（糖原的降解和糖原的生物合成（2 2学时）学时）14.214.2糖原代谢的调控糖原代谢的调控 （1 1学时）学时）第十五章第十五章 脂肪酸代谢（脂肪酸代谢（3 3学时）学时）第十六章第十六章 氨基酸的分解代谢（氨基酸的分解代谢（3 3学时）学时）第十七章第十七章 核酸代谢（核酸代谢（3 3学时）学时）11ppt课件What is Biochemistry?thestudyofthosemoleculesusedandmanufacturedbyliving things.12ppt课件Three aspects of biochemistry:1)Biochemistry is concerned with structural chemistry.It seeks to determine the structures of molecules found in living systems in order to understand structure-function relationships.Structural Biology13ppt课件2)Biochemistry is concerned with chemical change,this is reflected in the study of metabolic pathways Metabolism14ppt课件3)Biochemistry is concerned with information which has accumulated through evolution and is preserved in DNA(or sometimes RNA).Molecular BiologyThe Central Dogma15ppt课件Biochemistry through evolutionHow to build a life with molecules?Or The Molecular Design of Life16ppt课件胰岛素由A、B两个肽链组成。人胰岛素(InsulinHuman)A链有21个氨基酸，B链有30个氨基酸，共共51个氨基酸个氨基酸组成。其中A7(Cys)-B7(Cys)、A20(Cys)-B19(Cys)四个半胱氨酸中的巯基形成两个二硫键，使A、B两链连接起来。此外A链中A6(Cys)与A11(Cys)之间也存在一个二硫键。人工合成胰岛素人工合成胰岛素17ppt课件1958年，中国科学院在王应睐、曹天钦、邹承鲁、钮经义、沈年，中国科学院在王应睐、曹天钦、邹承鲁、钮经义、沈昭文等先生的带领下，提出了昭文等先生的带领下，提出了“世界上第一次用人工方法合成世界上第一次用人工方法合成的蛋白质在中华人民共和国实现的蛋白质在中华人民共和国实现”的宏伟目标。的宏伟目标。1959年初，人年初，人工合成胰岛素的工作全面展开。首先是由钮经义、沈昭文、龚工合成胰岛素的工作全面展开。首先是由钮经义、沈昭文、龚岳亭几位研究人员组织有关人员解决了氨基酸的大量供应问题。岳亭几位研究人员组织有关人员解决了氨基酸的大量供应问题。1965年，完成了结晶牛胰岛素的合成，它有着极为深远的意义。年，完成了结晶牛胰岛素的合成，它有着极为深远的意义。由于蛋白质和核酸两类生物高分子有生命现象中所起的主要作由于蛋白质和核酸两类生物高分子有生命现象中所起的主要作用，人工合成了第一个具有生物活力的蛋白质，便突破了一般用，人工合成了第一个具有生物活力的蛋白质，便突破了一般有机化合物领域到信息量集中的生物高分子领域之间的界限，有机化合物领域到信息量集中的生物高分子领域之间的界限，在人类认识生命现象的漫长过程中迈出了重要的一步。合成胰在人类认识生命现象的漫长过程中迈出了重要的一步。合成胰岛素工作的简报发表于岛素工作的简报发表于1965年年中国科学中国科学。18ppt课件Four transitions through evolution:1,chemicals,micromolecules 2,macrobiomolecules3,energy4,stress response19ppt课件The evolution of life required a series of transitions,beginning with the generation of organic molecules that could serve as the building blocks for complex biomolecules.20ppt课件The next major transition in the evolution of life was the formation of replicating molecules.Evolution Requires:1)Reproduction,2)Variation,3)Selective Pressure21ppt课件Variationwasintroducedbyanumberofmeans,fromsimplebasesubstitutionstotheduplicationofentiregenes.RNAappearstohavebeenanearlyreplicatingmolecule.Furthermore,someRNAmoleculespossesscatalyticactivity.However,therangeofreactionsthatRNAiscapableofcatalyzingislimited.Withtime,thecatalyticactivitywastransferredtoproteins,linearpolymersofthechemicallyversatileaminoacids.RNAdirectedthesynthesisoftheseproteinsandstilldoesinmodernorganismsthroughthedevelopmentofageneticcode,whichrelatesbasesequencetoaminoacidsequence.Eventually,RNAlostitsroleasthegenetothechemicallysimilarbutmorestablenucleicacidDNA.Inmodernorganisms,RNAstillservesasthelinkbetweenDNAandprotein.22ppt课件Energy Transformations Are Necessary to Sustain Living SystemsATPservesasthecellularenergycurrencythatlinksenergy-yieldingreactionswithenergy-requiringreactions.ATPitselfisaproductoftheoxidationoffuelmolecules,suchasaminoacidsandsugars.Withtheevolutionofmembraneshydrophobicbarriersthatdelineatethebordersofcellsiongradientswererequiredtopreventosmoticcrises.ThesegradientswereformedattheexpenseofATPhydrolysis.Later,iongradientsgeneratedbylightortheoxidationoffuelmoleculeswereusedtosynthesizeATP.23ppt课件Cells Can Respond to Changes in Their EnvironmentsThe final transition was the evolution of sensing and signaling mechanisms that enabled a cell to respond to changes in its environment.These signaling mechanisms eventually led to cell-cell communication,which allowed the development of more-complex organisms.The record of much of what has occurred since the formation of primitive organisms is written in the genomes of extant organisms.(molecular evolution)24ppt课件History of Biochemistry(up to 1982)25ppt课件1835 Jons Berzelius chemical catalysis,uses amylase(淀粉酶)as an example.1859 Charles Darwin publishes On the Origin of Species.1860 Louis Pasteur fermation catalyzed by enzymes,essence of yeast.1865 Gregor Mendel publishes his theory of genetics.1869 Fredrick Meischer discovers DNA in cell nuclei.1860 Eduard and Hans Buchner extracts materiel from yeast,conversion of glucose to alcohol.26ppt课件1914 Fritz Lipmann,the role of ATP in energy metabolism.1926 James Sumner,crystalline jack bean(刀豆)urease,is a protein.1926 Thomas Hunt Morgan writes The Theory of the Gene.1934 Arnold Beckman developes the first pH meter.1937 Hans Krebs discovers the citric acid cycle(TCA cycle).1941 George Beadle&Edward Tatum,the one-gene,one-enzyme hypothesis.Oswald Avery,Colin MacLeod,and Maclyn McCarthy DNA is the genetic material.27ppt课件1950 Edwin Chargaff A=T,G=C(Chargaffs rules).1952 Linus Pauling and Robert Corey -helix and the-pleated sheet 1953 James Watson and Frances Crick the double helix model of DNA.1953 Fredrick Sanger the first amino acid sequence of a protein(insulin).1956 Earl Sutherland isolates cyclic AMP.1957 Matthew Meselson and Franklin Stahl semiconservative DNA replication.28ppt课件1960 John Kendrew and Max Pertuz obtain the first 3-D structure of proteins(hemoglobin and myoglobin).1960 Jerald Huritz and Samuel Weiss discover RNA polymerase.1961 Francois Jacob and Jaques Monod propound the operon model of gene control.1963 Jean-Pierrre Changuex,F.Jacob,and J.Monod Allosteric model for inhibition of enzymes1964 Several groups Acrylamide gel electrophoresis of proteins is developed29ppt课件1965 Marshal Nirenberg,H.Gobind Khorana,and Severo Ochoa complete the elucidation of the genetic code1965 David Phillips 3-D model of first enzyme(lysozyme)1965 Robert Holley determines the structure of a transfer-aaRNA.1965 Jerome Vinograd discovers superhelical twisting.1968 Mark Ptashne and Walter Gilbert identify the first repressor genes1969 First synthesis of an enzyme(ribonuclease).30ppt课件1970 Hamilton Smith discovers restriction endonucleases.1970 Howard Temin and David Baltimore discover reverse transcriptase.1973 Stanley Cohen and Herbert Boyer prepare recombinant DNA.1974 Sung-Hou Kim,et al.produce the first X-ray structure of transfer RNA.1977 Cesar Milstein discovers how to produce monoclonal antibodies.1977 Allan Maxam and Walter Gilbert develop a chemistry for sequencing DNA.1977 Fredrick Sanger,S.Nicklen and A.R.Coulson develop a chemistry for sequencing DNA.1977 Phillip Sharp and Richard Roberts discover introns(intervening sequences).1982 Amzel LM,McKinney M,Narayanan P,Pedersen PL First x-ray structure of a membrane protein(9).31ppt课件1980s and early 1990sWonderful time for Molecular Biology32ppt课件Human Genome Project(1988-)Central Dogma(Crick F.1958)Molecular BiologyOmics:Metabolomics Transcriptomics ProteomicsStructural Genomics(1998-)Genomics33ppt课件TheeraofOmics:(1998-2003orlater?)Omics=Oh!Mix!(millenniumchaos?)34ppt课件What is Structural Genomics?It is an approach aiming at solving 3-D structures of the proteins encoded by an entire genome.Kim SH.Nature Structural Biology 199835ppt课件Original goals of SG:1,to establish a catalogue/library of all folds covering the entire protein universe2,to help the annotation of sequenced genomes36ppt课件International Structural Genomics ProjectsUSA and Canada:(1998-)9 NIH Structural Genomics CentersEU:France(3 centers:Paris-Sud,Marseille,Strasbourg)Germany(Structural Genomics Factory)UK(2 centers)(SPINE:Structural Proteomics in Europe,2001-)Asia:Japan(RIKEN)China(Yun-Yu SHI;Zihe RAO)(2002-)Korea:Israel:Weizmann Structural Proteomics Center37ppt课件Flow chart:1,Targets selection:Bioinformatics2,PCR and cloning:Molecular Biology3,Protein production:Biochemistry4,Data collection(X-ray diffraction/NMR)5,Structure determination:Structural Biology6,Function interpretation:General Biology38ppt课件Core characteristics:High throughput(hundreds to thousands samples)Large-scale(milligram level of protein sample)Multi-discipline integration(from molecular biology to structural biology)39ppt课件high throughputparallelization(平行化平行化)miniaturization(微量化微量化)automation(自动化自动化)40ppt课件cloning robot:500-1000 clones/3 dayscrystallization robot:96x3 drops/5 minprotein sample for crystallization trials in nanoliter volumes(10nl)Hansen CL.et al.PNAS;200241ppt课件TagSize(aa)ApplicationSequence or GenBank accession no.His6-10affinityHHHHHH(HH)T711 affinityASMTGGQQMGRS15affinityKETAAAKFERQHMDSArg1,5,6affinityRRRRR(R)CBP26affinityKRRWKKNFIAVSAANRFKKISSSGALFLAG4 or 8affinityDYKD or DYKDDDDKStrep 8affinityWSHPQFEKNusA491SET,affinityAccession no.AAN82367 MBP396SET,affinityAccession no.AAC43128 GST220SET,affinityAccession no.AAB59203 ZZ116SET,affinityAccession no.M74186TrxA109SETAccession no.AAC40210 Gb156SETAccession no.1MPEADsbADsbC208 236SETSETAccession no.P24991Accession no.P21892Different tags will make the difference 42ppt课件Different E.coli strains(DE3 series)BL21(DE3)BL21-pLysSBL21-codon-plusTuner RosettaRosetta-pLysSGoldStar43ppt课件Co-expression with chaperones(DnaK-DnaJ-GrpE and/or GroEL-GroES)Mainly works for those partially soluble targets Co-purification of chaperones with the target protein Re-aggregation/precipitation after removal of chaperones44ppt课件Eukaryotic expression systems(post-translational modifications)Pichia pastorisSaccharomyces cerevisiaeInsect cells(Sf9、SF21)Mammalian cells(CHO et al.)Virus-mediatedQuantity and Cost-effectivity45ppt课件DNA shufflingSaturation mutagenesisError-prone PCRTo improve:the solubility,activity and/or stabilityReetz,PNAS;2004in vitro/directed evolution46ppt课件Proteins samples for crystallization trials:1,pure and homogenous2,stable in solution of low salt concentration,proper pH and reductant(BME,DTT or TCEP)3,at high concentration(normally 10mg/ml)47ppt课件Hanging dropSitting drop48ppt课件49ppt课件Protein samples for NMR data collection:1,double labeling with 13C and 15N2,no oligomerization or aggregation3,stable for at least one week at RT or 4C4,high expression level(cost-effective)50ppt课件Optimization of xtals:1,about half of the xtals will not diffract at 3 or higher resolution2,parameters:salt concentration,buffer system,pH,divalent or trivalent irons3,precipitants:PEGs,MPD,salt,alcohol,4,ligands or substrates/products/analogs5,protein or nucleic acid partners 51ppt课件Data collection:X-ray diffraction:in-house X-ray generator synchrotron radiation acceleratorNMR spectrometry:500mHz,600mHz,800mHz 900mHz 52ppt课件in-house X-ray generator Data collection:synchrotron radiation accelerator53ppt课件 Assignment of function based on structural similarity Reciprocal stimulation and validation:biochemical assays versus structure analyses Structure-directed drug designFunction interpretation and application:54ppt课件 Assignment of function based on structural similarity3-D structureDALI comparisonClosest structuresSimilar molecular function?http:/www.ebi.ac.uk/dali55ppt课件Holm L,Kaariainen S,Rosenstrom P,Schenkel A.(2008)Searching protein structure databases with DaliLite v.3.Bioinformatics 24,2780-2781.56ppt课件 Reciprocal stimulation and validation:biochemical assays vs.structure analyses An example of licT from Bacillus substilis57ppt课件LicT mutant(active)H207D/H269DLicT wt(inactive)Comparison of licT-wt and licT mutantGraille*and Zhou*et al.JBC 2005 van Tilbeurgh et al.EMBO J.200158ppt课件Yang et al.EMBO J.20021122mRNA1122mRNAPKD=10MKD=1MCATPRD2PRD1RATCATRNA59ppt课件 Structure-directed drug designAn example of Thy1 from Thermotoga maritima Thy1:thymidylate synthase-complementing protein present in archaea,prokaryotes,viruses NOT in eukaryotesLesley,SA et al.PNAS;200260ppt课件Thy1-FAD-dUMP Thy1-dUMP-HEPES61ppt课件谷胱甘肽硫转移酶（谷胱甘肽硫转移酶（GSTGST）BiochemBiochem.J.(2001)360,1.J.(2001)360,11616XenobioticsXenobiotics（异型生物质，芳香族化合物）（异型生物质，芳香族化合物）GSH+Xenobiotics GSH+Xenobiotics GS-Xenobiotics GS-Xenobiotics毒性较强毒性较强溶解度低溶解度低体内富集体内富集毒性较弱毒性较弱溶解度高溶解度高解毒排毒解毒排毒62ppt课件GSTGST参与胞内氧化还原平衡维持，能防止芳香族有毒物质参与胞内氧化还原平衡维持，能防止芳香族有毒物质的体内富集，具有解毒功能。的体内富集，具有解毒功能。真核模式生物酿酒酵母中，有真核模式生物酿酒酵母中，有5 5个个GSTGST蛋白（蛋白（Gtt1Gtt1、Gtt2Gtt2、Gto1Gto1、Gto2Gto2、Gto3Gto3），但是没有一个的三维结构被解析，），但是没有一个的三维结构被解析，并且与已报道的序列相比，相似度较低。并且与已报道的序列相比，相似度较低。真菌界中的真菌界中的GSTGST蛋白家族分类很混乱，并且目前没有真菌蛋白家族分类很混乱，并且目前没有真菌的的GSTGST蛋白的三维结构被解析。蛋白的三维结构被解析。我们希望通过对我们希望通过对Gtt2Gtt2的研究，阐述清楚生化功能和反应机的研究，阐述清楚生化功能和反应机制，并对真菌中制，并对真菌中GSTGST的分类提供新的信息。的分类提供新的信息。Gtt2Gtt2的研究意义的研究意义63ppt课件Gtt2Gtt2的晶体的晶体Apo-formApo-form2.22.2埃埃GTS-bound formGTS-bound form磺化谷胱甘肽，磺化谷胱甘肽，2.22.2埃埃GSH-bound formGSH-bound form谷胱甘肽，谷胱甘肽，2.12.1埃埃64ppt课件Gtt2Gtt2的结构的结构溶液中为稳定二体，依靠静溶液中为稳定二体，依靠静电和疏水作用力维持电和疏水作用力维持每个单体含有两个结构域，每个单体含有两个结构域，N N端端Trx-likeTrx-like和和C C端全螺旋结构域端全螺旋结构域65ppt课件底物结合位点底物结合位点主要作用方式：氢键主要作用方式：氢键主要来源：主要来源：N N端结构端结构域的残基域的残基66ppt课件经典的催化残基在经典的催化残基在Gtt2Gtt2中缺失中缺失GSHGSH的硫原子周围既的硫原子周围既没有酪氨酸，也没有没有酪氨酸，也没有丝氨酸，更没有半胱丝氨酸，更没有半胱氨酸。氨酸。67ppt课件经典的三种催化类型经典的三种催化类型酪氨酸催化型酪氨酸催化型丝氨酸催化型丝氨酸催化型半胱氨酸催化型半胱氨酸催化型68ppt课件关键的催化残基：晶体结构的证据关键的催化残基：晶体结构的证据磺化谷胱甘肽磺化谷胱甘肽谷胱甘肽谷胱甘肽Apo-formApo-formSer129Ser129和和His133His133稳定的水分子很重要稳定的水分子很重要69ppt课件关键的催化残基：生化实验的证据关键的催化残基：生化实验的证据 突变了突变了水分子游离水分子游离活性下降活性下降70ppt课件还原经典的催化残基还原经典的催化残基空间结构比对空间结构比对突变突变T24T24，G27G27偶然突变导致偶然突变导致新的催化模式新的催化模式升高升高不变不变或或下降下降71ppt课件从结构上分析从结构上分析分析分析G27G27的微环境的微环境推测：空间位阻推测：空间位阻生化实验验证生化实验验证72ppt课件生化试验验证生化试验验证GlyGlyAlaAlaSerSerCysCysPhePhe活活性性下下降降侧侧链链体体积积增增大大73ppt课件GSTGST家族的生物信息学分析家族的生物信息学分析74ppt课件1.首次定义了一支新的首次定义了一支新的GST亚家族。亚家族。2.该亚家族具有与经典模式该亚家族具有与经典模式（Tyr-，Ser-，Cys-type）不同的一种新的催化位点。不同的一种新的催化位点。3.Gtt2是首次报道的来源于是首次报道的来源于真菌的真菌的GST蛋白结构，为蛋白结构，为目前混乱的真菌目前混乱的真菌GST蛋白蛋白分类提供了新的思路。分类提供了新的思路。Ma XX et al.EMBO Reports 200975ppt课件http:/www.rcsb.org/pdb/home/home.do76ppt课件ProteinsNucleic AcidsProtein/NA ComplexesOtherTotalX-ray48003 1167 2196 17 51383 NMR6982 869 149 6 8006 Electron Microscopy171 16 65 0 252 Hybrid15 1 1 1 18 Other114 4 4 9 131 Total55285 2057 2415 33 59790Last update:Tuesday Sep 01,2009 77ppt课件X-rayLastupdate:Tuesday Sep 01,200978ppt课件NMR79ppt课件Electron Microscopy80ppt课件GrowthOfUniqueFoldsPerYearAsDefinedBySCOP81ppt课件Future orientations of SG1,Reconstruction of multiprotein complexes (based on interactomics)2,Systematically solving the 3-D structures of membrane proteins (a challenge of novel techniques)3,Systems Biology 82ppt课件Interactomes:1,Yeast two-hybrid2,TAP(tandem affinity purification)3,Mass Spectrometry4,Co-IP(coimmunoprecipitation)5,Phage display83ppt课件Overexpress the putative protein complex in vivoor Reconstruct it in vitro from the individual proteinsSolve the 3-D structure by means of X-ray crystallography Cryo-Electron Microscopy Electron crystallography(2D EM)Electron tomography84ppt课件Systematically Structure the Membrane Proteins:A big challenge!PDB:59,790 structures,updated on 2009/09/01http:/www.rcsb.org/pdb/index.html 85ppt课件86ppt课件Unique proteins*in database=202.Number of cordinate files in database=551.*Includesproteinsofsametypefromdifferentspecies.Forexample,photosyntheticreactioncentersfromR.viridisandR.sphaeroidesareconsideredunique.Lastdatabaseupdate:22Aug200987ppt课件88ppt课件Systems Biology(系统生物学系统生物学):1,Conceptually,an emergent field that aims at system-level understanding of biological systems.(http:/www.systems-biology.org)2,In practice,a combination of omic approaches,data integration,modeling and synthetic biology.(Ge at al.TIG,2003)89ppt课件Hypothesis-driven research in systems biologyKitano H.Science;200290ppt课件GenomicsStructural GenomicsInteractomicsSystems BiologyWordsSentencesLiteraturesDNA seqencesProtein FunctionsInteraction NetworksSystemsParagraphsIdea originated from Sali et al Nature 200391ppt课件Molecular BiologySystems BiologyIntegration&ReconstructionReduction(molecular functions)Massive Data(GenBank,PDB et al.)Digital transparent systema dream to be realized92ppt课件