理学类分子生物物理学 (2)优秀PPT.ppt

理学类分子生物物理学你现在浏览的是第一页，共81页分子水平分子水平结构结构功能功能研究生物体系物理学性质、行为研究生物体系物理学性质、行为你现在浏览的是第二页，共81页Biopolymers:Nucleic acid(DNA,RNA)ProteinMoleculesinBiosystemSaccharideLipidOther你现在浏览的是第三页，共81页PROTEINSTRUCTURE你现在浏览的是第四页，共81页 19651965年中国在世界上首次用化学方法年中国在世界上首次用化学方法人工合成的蛋白质人工合成的蛋白质牛胰岛素牛胰岛素你现在浏览的是第五页，共81页SecondaryStructurePrimaryStructureTertiaryStructuresupersecondaryStructureormotifdomainQuaternaryStructureHierarchyofProteinStructureby Linderstrm-Lang你现在浏览的是第六页，共81页ChiralLalanineCOOHCH3NH2HPropertyofaminoacid你现在浏览的是第七页，共81页zwitterionUnchargedstructureMinorcomponentDipolarion,orzwitterionMajorcomponent你现在浏览的是第八页，共81页Classificatoryofaminoacidbasedsidechains(Rgroups)Non-polarG,A,V,L,I;F,W,P,M,PolarneutralS,T,N,QacidicD,E;C,Y basicR,K,H你现在浏览的是第九页，共81页?Histidine你现在浏览的是第十页，共81页ProteinPrimaryStructure你现在浏览的是第十一页，共81页Peptide bondBackboneSide chain Amine/N terminusCarboxyl/C terminus你现在浏览的是第十二页，共81页 Pauling&Corey0.132nmC-N,0.149nmC=N,0.127nm你现在浏览的是第十三页，共81页 =180 =180=0 =0?CCN,C你现在浏览的是第十四页，共81页 CONHC3.20(3.0)2.80(2.70)2.90(2.80)2.40(2.20)O2.70(2.60)2.70(2.60)2.40(2.20)N2.70(2.60)2.40(2.20)H2.00(1.90)MinimalDistance()betweennonbondingatom(G.N.Ramachandran)你现在浏览的是第十五页，共81页phi(F F),psi(Y Y),andomega(W)W)你现在浏览的是第十六页，共81页 interactionRelation with Energy and distancecharger-charger-1charger-dipoler-2dipole-dipoler-3charge-induced dipoler-4dipole-induced dipoler-6Transient dipole-induced dipoler-6Relation with Energy and distance你现在浏览的是第十七页，共81页 VanderWaalsforce Lennard-Jonespotential10kJmol-1，range:0.30.5nm 你现在浏览的是第十八页，共81页H-bond definition,H-bond location OO.H.H-X XHydrogenbond OOHHX XHydrogen bonds can vary in strength from very weak(1-2 kJ mol1)to extremely strong(40 kJ mol1),so strong as to be indistinguishable from a covalent bond,as in the ion HF2.Typical values include:OH.:N(7 kcal/mol)OH.:O(5 kcal/mol)NH.:N(3 kcal/mol)NH.:O(2 kcal/mol)你现在浏览的是第十九页，共81页ProteinSecondary Structure你现在浏览的是第二十页，共81页你现在浏览的是第二十一页，共81页 1951,PaulingPZ0=-57=-47p=0.54nmz0=0.15nm你现在浏览的是第二十二页，共81页Helicesrepetitive secondary structureN NC CHelices are the most abundant form of secondary structure containing approximately 32-38%of the residues in globular proteins(Kabsch and Sander,1983)a a-helix310helixp p-helix你现在浏览的是第二十三页，共81页 nrP3.613-57-473.60.1540.55310-49-263.00.2000.60-57-74.40.1150.51Paral-119+1132.00.3200.64Antiparal-139+1352.00.3400.68Parametersofsecondarystructuren is the number of residues per helical turnr is the helical rise per residue(nm)p is the helical pitch(nm).你现在浏览的是第二十四页，共81页 H-bondAtoms in H-bond loopradius3.613i,i+4132.3310i,i+3101.9i,i+5162.8Parametersofsecondarystructure你现在浏览的是第二十五页，共81页a a-helixintroduction32-38%of all residues in globular proteins The average length of an alpha helix is 10 residues.Found(-64+/-7,-41+/-7)/ideal(-57.8,-47.0)The structure repeats itself every 5.4 along the helix axis,i.e.we say that the a-helix has a pitch of 5.4.你现在浏览的是第二十六页，共81页a-helices have 3.6 amino acid residues per turn,i.e.a helix 36 amino acids long would form 10 turns.The separation of residues along the helix axis is 5.4/3.6 or 1.5,i.e.the a-helix has a rise per residue of 1.5 你现在浏览的是第二十七页，共81页the phi and psi angles of the alpha helix lie in the center of an allowed,minimum energy region of the Ramachandran(phi,psi)map.Whyalpha-helixisabundantinnativeglobularprotein?你现在浏览的是第二十八页，共81页the dipoles of hydrogen bonding backbone atoms are in near perfect alignment.你现在浏览的是第二十九页，共81页the radius(2.3 angstrom)of the helix allows for favorable van der Waals interactions across the helical axis side chains are well staggered minimizing steric interference你现在浏览的是第三十页，共81页CO group toward carboxyl terminusNH group toward amide terminusH-bond,i-(i+4)Side chain:i-(i+3);i-(i+4)interactions between i and i+4 stabilize helix你现在浏览的是第三十一页，共81页Distortions of a a-helices Themajorityofa a-helicesinglobularproteinsarecurvedordistortedsomewhatcomparedwiththestandardPauling-Coreymodel.Why?1.The packing of buried helices against other secondary structure elements in the core of the protein2.Proline residues induce distortions of around 20 degrees in the direction of the helix axis3.Solvent.Exposed helices are often bent away from the solvent region.This is because the exposed C=O groups tend to point towards solvent to maximise their H-bonding capacity,i.e.tend to form H-bonds to solvent as well as N-H groups.你现在浏览的是第三十二页，共81页310helixintroductionOnly3.4%oftheresiduesareinvolvedin310helices,andnearlyallthoseinhelicalsegmentscontainingi-i+3hydrogenbonds.Ideal(-74.0,-4.0)/found(-71.0and-18.0)CO-HNhydrogenbond:i-i+3你现在浏览的是第三十三页，共81页Standard 310 helix你现在浏览的是第三十四页，共81页ProlinehelixLeft handed helix3.0 residues per turnpitch=9.4 No hydrogen bonding in the backbone but helix still forms.Poly-glycine also forms this type of helixCollagen:highinGly-Proresidueshasthistypeofhelicalstructure你现在浏览的是第三十五页，共81页p p-helicesintroductionThe pi helix is an extremely rare secondary structural element in proteins.the backbone C=O of residue i hydrogen bonds to the backbone HN of residue i+5.i-i+5H-bonds2.8angstrom你现在浏览的是第三十六页，共81页1.the phi and psi angles of the pure pi helix(-57.1,-69.7)lie at the very edge of an allowed,minimum energy region of the Ramachandran(phi,psi)map.2.the pi helix requires that the angle tau(N-Ca-C)be larger(114.9)than the standard tetrahedral angle of 109.5 degrees.3.the large radius of the pi helix means the polypeptide backbone is no longer in van der Waals contact across the helical axis forming an axial hole too small for solvent water to fill.4.side chains are more staggered than the ideal 3.10 helix but not as well as the alpha helix.你现在浏览的是第三十七页，共81页H-bond:1-5你现在浏览的是第三十八页，共81页alpha-helix,surface of protein,barrieramphiphilicproteindesign projects by Degrado,USAHelicalwheeltools你现在浏览的是第三十九页，共81页HelixdipoleThe partial charges on the amide hydrogen and carbonyl oxygen are shown in units of the elementary charge contributing to an overall dipole moment of 3.46 Debye units.helixmacrodipole你现在浏览的是第四十页，共81页Sheet20-28%(Kabsch&Sander,1983;Creighton,1993)a repeating secondary structure你现在浏览的是第四十一页，共81页 nrP3.613-57-473.60.1540.55310-49-263.00.2000.60-57-74.40.1150.51Paral-119+1132.00.3200.64Antiparal-139+1352.00.3400.68Parametersofsecondarystructuren is the number of residues per helical turnr is the helical rise per residue(nm)p is the helical pitch(nm).你现在浏览的是第四十二页，共81页-139 and+135 你现在浏览的是第四十三页，共81页ParallelsheetAntiparallelsheet你现在浏览的是第四十四页，共81页你现在浏览的是第四十五页，共81页你现在浏览的是第四十六页，共81页你现在浏览的是第四十七页，共81页Twistsabout 30 degrees per residue in right-handed senseLeft-handed:crossover angelRight-handed:progressive H-bond twist你现在浏览的是第四十八页，共81页Parallel sheets are less twisted than anti-parallel and are always buried.你现在浏览的是第四十九页，共81页BulgesBeta-hairpinCrossover connection:right-handed left-handedOne residue backbone,two H-bondsStrandconnections你现在浏览的是第五十页，共81页Turn1.that serve to reverse the direction of the polypeptide chain 2.Surface of the protein3.Antibody recognition,phosphorylation,glycosylation,hydroxylation 你现在浏览的是第五十一页，共81页Gamma-turn1.H-bond:i-i+22.(70,-60)and(-70,60)for i+1 residue你现在浏览的是第五十二页，共81页TypeIandIturn1.H-bond:i-i+32.(-60,-30)and(-90,0)for i+1,i+2 residues你现在浏览的是第五十三页，共81页The backbone dihedral angles of residue are(-60,120)and(80,0)of residues i+1 and i+2,respectively of the type II turn.2.3.3.TypeIIandIIturn你现在浏览的是第五十四页，共81页the hydrogen bond between CO of residue i and NH of residue i+3.This is a single turn of right-handed(III)and left-handed(III)3.10 helix,respectively.The backbone dihedral angles of residue are(-60,-30)and(-60,-30)of residues i+1 and i+2,respectively of the classical type III turn.你现在浏览的是第五十五页，共81页2.3.4.Otherstructures1.Loop random coil2.Paperclips cap of a-helix你现在浏览的是第五十六页，共81页Identificationofsecondarystructure你现在浏览的是第五十七页，共81页Identificationwithout3DstructureCD可信度：可信度：a-helix,97%;sheet 75%;50%turn,89%otherFrom Manavalan&Johnson,1987你现在浏览的是第五十八页，共81页FTIRamide band I 1600-1700你现在浏览的是第五十九页，共81页NMR couplingconstant:3JHAHN right-handed a-helix,phi=-57,3JHAHN=3.9 Hz right handed 3.10 helix,phi=-60,3JHAHN=4.2 Hz antiparallel-sheet,phi=-139,3JHAHN=8.9 Hz parallel-sheet,phi=-119,3JHAHN=9.7 Hz left-handed a-helix,phi=57,3JHAHN=6.9 Hz你现在浏览的是第六十页，共81页PredictionofsecondarystructurePredictionofsecondarystructure(a).Homology.If sequence 25-30%,structure similarity(b).Statistical.Chou&Fasman(1978).(c).Stereochemical SchifferandEdmundson(1967)你现在浏览的是第六十一页，共81页Motif&domain你现在浏览的是第六十二页，共81页超二级结构超二级结构超二级结构超二级结构motifmotif相邻的二级结构单元组合在一起，相邻的二级结构单元组合在一起，彼此相互作用，排列形成规则的、彼此相互作用，排列形成规则的、在空间结构上能够辨认的二级结构在空间结构上能够辨认的二级结构组合体，并充当三级结构的构件组合体，并充当三级结构的构件（block building)，成为超二级结，成为超二级结构，介于二级结构与结构域之间的构，介于二级结构与结构域之间的结构层次。结构层次。你现在浏览的是第六十三页，共81页常见的几种超二级结构形式常见的几种超二级结构形式常见的几种超二级结构形式常见的几种超二级结构形式a.a.-loop-loop-;b.;b.-;c.;c.-loop-loop-;d.Rossmann;d.Rossmann折叠；折叠；折叠；折叠；E,f,g.E,f,g.回形拓扑结构回形拓扑结构回形拓扑结构回形拓扑结构你现在浏览的是第六十四页，共81页 细胞色素细胞色素C-loop-你现在浏览的是第六十五页，共81页 细胞核抗原的细胞核抗原的-结构结构-你现在浏览的是第六十六页，共81页 纤溶酶原的纤溶酶原的-loop-结构结构你现在浏览的是第六十七页，共81页结构域结构域domain多肽链在超二级结构的基础上进一步多肽链在超二级结构的基础上进一步折叠成紧密的近乎于球状的结构，这折叠成紧密的近乎于球状的结构，这种结构称为结构域种结构称为结构域domain你现在浏览的是第六十八页，共81页你现在浏览的是第六十九页，共81页你现在浏览的是第七十页，共81页 结构域的特点结构域的特点（1）结构域是球状蛋白质的独立折叠单位。对一些较小的球状蛋白质分子或亚基来说，结构域和三级结构是一个意思。例如红氧还蛋白，核糖核酸酶、肌红蛋白等。你现在浏览的是第七十一页，共81页 （2）对于较大的球状蛋白质或亚基，其三级结构往往由两个或多个结构域缔合而成也即它们是多结构域的，例如免疫球蛋白的轻链含2个结构域。你现在浏览的是第七十二页，共81页 结构域有时也指功能域。功能域可以是一个结构域，也可以是由两个结构域或两个以上结构域组成，从功能角度看许多多结构域的酶，其活性中心都位于结构域之间，因为通过结构域容易构建具有特定三维排布的活性中心。结构域之间常常只有一段柔性的肽链连接，形成所谓铰链区，使结构域容易发生相对运动，这是结构域的一大特点。结构域之间的这种柔性将有利于活性中心结合底物和施加应力。你现在浏览的是第七十三页，共81页Protein Tertiary Structure你现在浏览的是第七十四页，共81页三级结构指一个不可分的单元（分子）的完整的三维空间结构。对于蛋白质，此单元通常是共价连接的一个分子。目前已经测出三级结构的生物大分子目前已经测出三级结构的生物大分子都储存在蛋白质数据库中（都储存在蛋白质数据库中（Protein data bank,PDB)，借助软件可查阅显，借助软件可查阅显示其空间结构，还可以在不同方向旋示其空间结构，还可以在不同方向旋转以获得空间结构的细节。转以获得空间结构的细节。你现在浏览的是第七十五页，共81页嗜热菌蛋白酶与人碳酸酐酶的结构图嗜热菌蛋白酶与人碳酸酐酶的结构图嗜热菌蛋白酶与人碳酸酐酶的结构图嗜热菌蛋白酶与人碳酸酐酶的结构图你现在浏览的是第七十六页，共81页研究蛋白质三级结构的方法研究蛋白质三级结构的方法X射线晶体衍射（X-raycrystallography)多维核磁共振(multi-dimensionalNMR)三维电子显微镜技术（3-dimensiionalEM)扫描探针显微术(ScanningProbeMicroscopy,SPM)你现在浏览的是第七十七页，共81页ProteinQuaternaryStructure你现在浏览的是第七十八页，共81页 独立的三级结构之间的非独立的三级结构之间的非共价缔合称为四级结构。这些共价缔合称为四级结构。这些独立的三级结构称为亚基或亚独立的三级结构称为亚基或亚单位。单位。你现在浏览的是第七十九页，共81页你现在浏览的是第八十页，共81页更多资源初一语文初一英语初一数学初一政治初一历史初一地理初一生物你现在浏览的是第八十一页，共81页