Lec7aminoacidspeptidesandproteinsst

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1、Amino Acids,Peptides,and Amino Acids,Peptides,and ProteinsProteinsThe light produced by fireflies is the result of a reaction involving the protein luciferin and ATP,catalyzed by the enzyme luciferase.Erythrocytes contain large amounts of the oxygen-transporting protein hemoglobin.The protein kerati

2、n,formed by all vertebrates,is the chief structural component of hair,scales,horn,wool,nails,and feathers.2分布广：分布广：所有器官、组织都含有蛋白质；细胞的各个部所有器官、组织都含有蛋白质；细胞的各个部分都含有蛋白质。分都含有蛋白质。含量高：含量高：蛋白质是细胞内最丰富的有机分子，占人体干蛋白质是细胞内最丰富的有机分子，占人体干重的重的4545，某些组织含量更高，例如脾、肺及，某些组织含量更高，例如脾、肺及横纹肌等高达横纹肌等高达8080。蛋白质具有重要的生物学功能：蛋白质具有重要的生物

3、学功能：1 1）作为生物催化剂（酶）作为生物催化剂（酶）2 2）代谢调节作用）代谢调节作用 3 3）免疫保护作用）免疫保护作用 4 4）物质的转运和存储）物质的转运和存储 5 5）运动与支持作用）运动与支持作用 6 6）参与细胞间信息传递）参与细胞间信息传递 。1.Biology catalytic activityEnzymes3a.To regulate the ability of other proteins a.To regulate the ability of other proteins hormones:insulin(hormones:insulin(胰岛素胰岛素)soma

4、totropin(somatotropin(生长激素生长激素)thyrotropin(thyrotropin(促甲状腺素）促甲状腺素）b.To regulate the gene expressionb.To regulate the gene expression positively:AP1 positively:AP1 negatively:NF1 negatively:NF1 lac lac repressor (repressor (乳糖抑制体乳糖抑制体)2.Biological Regulation ActivityRegulatory proteins 4Lac represso

5、r DNA-binding domain(Helix-turn-helix motif)AP-1 bound to a DNA oligomer (Leucine zipper motif)5Lac repressor inhibits the expression of genes coding for proteins involved in the metabolism of lactose in bacteria.AP-1 upregulates transcription of genes containing the TPA DNA response element3.Transp

6、ort FunctionTransport Proteins a.Transport within or between different cells or tissuesb.Transport into or out of cellsHemoglobin Membrane Transport Protein 6Storage proteins serve as reservesof metal ions and amino acidsovalbumin （卵清白蛋白）（卵清白蛋白）casein （酪蛋白）（酪蛋白）zein （玉米蛋白）（玉米蛋白）ferritin （铁蛋白）（铁蛋白）4.

7、Storage FunctionStorage Proteins Casein micelle in milk(82%)Zein is the storage protein in corn kernels.Ferritin molecules store thousands of iron atoms within their mineral core7Motor protein kinesin (驱动蛋白）Contractile and Motile Proteins actin （肌动蛋白）myosin（肌球蛋白）tubulin（微管蛋白）5.Motor Function Motor p

8、rotein-dependent movement of cargo.Structure of skeletal muscle.8 collagen（胶原蛋白）（胶原蛋白）elastin（弹性蛋白）（弹性蛋白）keratin（角蛋白）（角蛋白）fibroin （蚕丝蛋白）（蚕丝蛋白）proteoglycan（蛋白聚糖）（蛋白聚糖）6.Structural component Structural Proteins 9a.A kind of proteins involving in the complex pathways of cellular response to hormones an

9、d growth factors:IRS-1(insulin receptor substrate)b.Anchoring proteins:AKAP(a kinase anchoring proteins)7.Scaffold Function Scaffold Proteins(Adapter proteins)The intramolecular phosphorylation of the AKAP domain of AKAP250 in response to and mediated by the association with 2AR10immunoglobulins（免疫球

10、蛋白）（免疫球蛋白）blood-clotting proteins thrombin（凝血酶）（凝血酶）fibrinogen（纤维蛋白原）（纤维蛋白原）antifreeze protein （抗冻蛋白）（抗冻蛋白）lytic and neurotoxic proteins snake and bee venoms（毒液）（毒液）ricin(蓖麻毒素）蓖麻毒素）diphtheria（白喉毒素）白喉毒素）8.Protective and attack Protective and Exploitive Proteins 11 Proteins are linear polymers of 20 d

11、ifferent amino acids They are the embodiment of the transition from one-dimensional world of sequences to the three dimensional world of molecules capable of diverse activities.Protein structure and functionDNA replication machinery can make DNA copy without dissociation12 The 20 amino acids bestow

12、specific functional properties on the polymer(protein)Proteins interact with other macromolecules Protein function correlates with flexibility Protein structure and functionA complex protein assemblyUpon binding iron,the protein lactoferrin undergoes conformational changes13Chains of amino acids in

13、a specific sequence(primary structure)define a protein like insulin.These chains fold into well-defined structures(tertiary structure).Such structures assemble with other chains to form arrays such as the complex of six insulin molecules(quarternary structure).Protein structure and function From pri

14、mary structure to quaternary structure 14The functions of protein arise from specific binding interactions and conformationalchanges in the structure of a properly folded protein.15Protein are built from a repertoire of 20 amino acidsAn-amino acid consists of a central carbon atom,linked to an amino

15、 group,a carboxylic acid group,a hydrogen atom,and a distinct side chain R group.Amino Acid16With four different groups connected to the tetrahedral-carbon atom,-amino acids are Chiral:two mirror image forms are called L isomer and D isomer.The-amino carboxylic acids(amino acids)can be of two stereo

16、isomers17Only L isomer are found in proteins.All L amino acids have an absolute S(rather than R)configuration.The counterclockwise direction from the highest to lowest substituents18氨基酸的分类和结构氨基酸的分类和结构（1）根据氨基酸的化学结构分为：脂肪族，芳香族和杂环族三类。（2）根据氨基酸的R基极性分为：非极性R基氨基酸，不带电荷极性氨基酸，带电荷极性氨基酸（3）根据氨基酸分子中所含氨基和羧基数目的不同分：中性

17、、碱性、酸性氨基酸（4）根据氨基酸的R基物理性质，与水的相互作用分为：疏水氨基酸，亲水氨基酸 The remarkable range of functions mediates by proteins results from the diversity and versatility of 20 amino acids19 Nonpolar,Aliphatic R groups(7)Amino Acids Can Be Classified by R GroupThe larger aliphatic side chains are hydrophobic-that is,they ten

18、d to cluster together rather than contact to water.Hydrophobic amino acidsGlycine is the simplest,and being achiral.甘氨酸甘氨酸 丙氨酸丙氨酸 脯氨酸脯氨酸 缬氨酸缬氨酸亮氨酸亮氨酸 异亮氨酸异亮氨酸 甲硫氨酸甲硫氨酸20The side chain of proline is bonded to both the nitrogen and the -carbon atoms.Proline markedly influences protein architecture bec

19、ause its ring structure makes it more conformationally restricted than the other amino acidsProline a very“special”amino acid21 Aromatic R groups(3)Amino Acids Can Be Classified by R GroupAromatic acids can absorb ultraviolet light苯丙氨酸苯丙氨酸 酪氨酸酪氨酸 色氨酸色氨酸2223色氨酸、酪氨酸的最大吸收峰在色氨酸、酪氨酸的最大吸收峰在 280nm 附近。附近。大多

20、数蛋白质含有这两种氨基酸残基，所以测定蛋白大多数蛋白质含有这两种氨基酸残基，所以测定蛋白质溶液质溶液280nm的光吸收值是分析溶液中蛋白质含量的快速的光吸收值是分析溶液中蛋白质含量的快速简便的方法。简便的方法。Polar,uncharged R groups(5)Amino Acids Can Be Classified by R GroupSerine and threonine contain hydroxyl groups.Cysteine contain a sulfhydryl/thiol group.Asparagine and glutamine contain amide gr

21、oups.丝氨酸丝氨酸 苏氨酸苏氨酸 半胱氨酸半胱氨酸天冬酰胺天冬酰胺 谷氨酰胺谷氨酰胺24多肽链上的两个半胱氨酸分子或残基可以以二硫键相连（多肽链上的两个半胱氨酸分子或残基可以以二硫键相连（e.g.e.g.胰岛胰岛素）素）二硫键连接的残基有强的疏水性（非极性）二硫键连接的残基有强的疏水性（非极性）二硫键在两个不同蛋白质链间或蛋白质分子内的不同部分形成共价二硫键在两个不同蛋白质链间或蛋白质分子内的不同部分形成共价连接，在许多蛋白质结构中扮演着重要的角色（连接，在许多蛋白质结构中扮演着重要的角色（e.g.e.g.稳定蛋白结构）稳定蛋白结构）25 Positively charged R grou

22、ps(3)Amino Acids Can Be Classified by R GroupAt neutral pH,lysine and arginine are positive charged.With a pKa value near 6,Histidine can binds or release protons near physiological pH.Histidine is often found in the active site.赖氨酸赖氨酸 精氨酸精氨酸 组氨酸组氨酸26 Negatively charged R groups(2)Amino Acids Can Be

23、 Classified by R GroupAspartate and glutamate are hydrolyzed products of asparagine and glutamine by acid or base,respectively.In some proteins,acidic amino acids accept protons,and this ability is often functionally important.天冬氨酸天冬氨酸 谷氨酸谷氨酸27Abbreviations for Amino AcidsAmino acids are often desig

24、nated by either a three-letter abbreviation or a one-letter symbol28Uncommon Amino Acids Also Have Important Functions4-羟脯氨酸羟脯氨酸5-羟赖氨酸羟赖氨酸6-N-甲基赖氨酸甲基赖氨酸-羧基谷氨酸羧基谷氨酸锁链赖氨素锁链赖氨素硒代半胱氨酸硒代半胱氨酸鸟氨酸鸟氨酸瓜氨酸瓜氨酸29The ionization state of amino acids is altered by a change in pH.The zwitterionic form predominates n

25、ear physiological.Amino acids are zwitterions30 1.1.当外液当外液pHpH为某一为某一pHpH值时，氨基酸分子中所含的值时，氨基酸分子中所含的-NHNH3 3+和和-COO-COO-数目正好相等，净电荷为数目正好相等，净电荷为0 0。这一。这一pHpH值值即为氨基酸的即为氨基酸的等电点，简称等电点，简称pIpI。2.2.某氨基酸的等电点即为该氨基酸某氨基酸的等电点即为该氨基酸两性离子两性离子两边两边的的pKpK值和的一半。值和的一半。3.3.在氨基酸等电点以上任何在氨基酸等电点以上任何pHpH，AAAA带净的负电荷带净的负电荷，在电场中向阳极移

26、动；在氨基酸等电点以下任，在电场中向阳极移动；在氨基酸等电点以下任何何pHpH，AAAA带净的正电荷，在电场中向阴极移动。带净的正电荷，在电场中向阴极移动。4.4.在一定在一定pHpH范围中，溶液的范围中，溶液的pHpH离离AAAA等电点愈远，等电点愈远，AAAA带净电荷愈多。带净电荷愈多。等电点等电点 pI3132pH=pI+OH-pHpI+H+OH-+H+pHpI氨基酸的兼性离子氨基酸的兼性离子 阳离子阳离子阴离子阴离子CHNH2COOHR CHNH2COOHRCHNH3+COO-R CHNH3+COO-RCHNH2COO-R CHNH2COO-RCH COOHRNH3+CH COOHRN

27、H3+Amino Acids Have Characteristic Titration Curves1GlyHGlyKo2oGlyHGlyK221GlyGlyHKKAt isoelectric point Gly-=Gly+K1 K2=H+2 H+=(K1 K2)1/2 I=(K1 K2)1/2 pI=(p K1+p K2)/2 Gly pI=(2.34+9.60)/2=5.97缓冲区缓冲区33甘氨酸离子基团的甘氨酸离子基团的p pK Ka a 值小于那些被简单的甲基取代的氨基或羧基。值小于那些被简单的甲基取代的氨基或羧基。这一这一p pK Ka a值得受扰下调是由于分子间的相互作用。电性相

28、斥导致兼性离子不值得受扰下调是由于分子间的相互作用。电性相斥导致兼性离子不稳定，推动平衡向右进行。稳定，推动平衡向右进行。氨基与离去的质子氨基与离去的质子之间的相互排斥使之间的相互排斥使羧基羧基的的p pK Ka a 减小减小羧基中带负电荷的氧原子将电子羧基中带负电荷的氧原子将电子从氨基拉过来，使氨基从氨基拉过来，使氨基的的p pK Ka a 减小减小34pI=（pK1+pKR）/2 =（2.19+4.25)/2 =3.22 35pI=（pK2+pKR）/2 =（6.0+9.17）/2 =7.5936 带点状态判定带点状态判定 pI pH 0 pI pH 0 pI pH 0 带正电带正电 pI

29、 pH=0 pI pH=0 不带电不带电 等电点的计算等电点的计算 侧链为非极性基团或虽为极性基团但不解离的侧链为非极性基团或虽为极性基团但不解离的AAAA：pI=(pKpI=(pK1 1+pK+pK2 2)酸性酸性AA(Glu,Asp,Cys)AA(Glu,Asp,Cys)：pI=(pKpI=(pK1 1+pK+pKR R)碱性碱性AA(lys,Arg,His)AA(lys,Arg,His)：pI=(pKpI=(pKR R+pK+pK2 2)37等电点等电点 pISeven of the 20 amino acids have readily ionizable side chains.1.

30、82.48.811.0Only histidine has an R group(pKa 6.0)providing significant buffering power near the neutral pH usually found in the intracellular and extracellular fluids of most animals and bacteria.38Peptides Are Chains of Amino AcidsProteins are linear polymers by linking the-carboxyl group of one am

31、ino acid to the-amino group of another amino acid with a peptide bond.The formation of a dipeptide is accompanied by the loss of a water,and requires an input of free energy.Peptide bonds are quite stable kinetically,because of high activation energy.A polypeptide chain consist of regularly repeatin

32、g part,main chain/backbone.The backbone is rich in hydrogen-bonding potential.3940*肽肽是由氨基酸通过肽键缩合而形成的化合物。是由氨基酸通过肽键缩合而形成的化合物。*两分子氨基酸缩合形成两分子氨基酸缩合形成二肽二肽，三分子氨基酸缩，三分子氨基酸缩合则形成合则形成三肽三肽*肽链中的氨基酸分子因为脱水缩合而基团不全，肽链中的氨基酸分子因为脱水缩合而基团不全，被称为被称为氨基酸残基氨基酸残基(residue)。氨基酸残基的氨氨基酸残基的氨基上缺了一个氢，羧基上缺了一个羟基。基上缺了一个氢，羧基上缺了一个羟基。*由十个以

33、内氨基酸相连而成的肽称为由十个以内氨基酸相连而成的肽称为寡肽寡肽(oligopeptide)，由更多的氨基酸相连形成的肽由更多的氨基酸相连形成的肽称称多肽多肽(polypeptide)。A polypeptide chain has polarity五肽：五肽：YGGFL，亮氨，亮氨酸酸-脑腓肽，是一个脑腓肽，是一个类压片的肽，可以调类压片的肽，可以调节疼痛的感知。节疼痛的感知。如果把它反过来，如果把它反过来，LGFFY,就是另一个不就是另一个不同的分子，不具备这同的分子，不具备这个特性。个特性。41 一条多肽链有一个氨基端和一个羧基端。氨基端被视为一个一条多肽链有一个氨基端和一个羧基端。氨基

34、端被视为一个多肽链的开始。多肽链的开始。氨基末端（氨基末端（amino terminal）或）或 N 末端末端：多肽链中有：多肽链中有自由氨基自由氨基的一端的一端 羧基末端（羧基末端（carboxyl terminal）或）或C 末端：末端：多肽链中有多肽链中有自由羧基自由羧基的一端的一端 多肽的酸碱表现可从它游离多肽的酸碱表现可从它游离-氨基和氨基和-羧基以及可电离的羧基以及可电离的R R基团的性质和数量来预测基团的性质和数量来预测 当氨基酸成为多肽中的一个残当氨基酸成为多肽中的一个残基时，其离子化基时，其离子化R R基团的基团的p pK Ka a可能有一定程度的变化可能有一定程度的变化Pe

35、ptides Can Be Distinguished by Their Ionization Behavior丙氨酰谷氨酰甘氨酰赖氨酸丙氨酰谷氨酰甘氨酰赖氨酸42氨基酸残基的相对平均分子质量是氨基酸残基的相对平均分子质量是110110，可通过残基数粗略计算蛋白质的分子质量。，可通过残基数粗略计算蛋白质的分子质量。含有两条或多条肽链含有两条或多条肽链 ，以非共价键结合的蛋白质称为多亚基，以非共价键结合的蛋白质称为多亚基 (multisubunit)(multisubunit)蛋白质。蛋白质。如果含有两个以上相同的亚基，该蛋白质称作寡聚如果含有两个以上相同的亚基，该蛋白质称作寡聚 (oligom

36、eric)(oligomeric)蛋白质。蛋白质。43Polypeptides Have Characteristic Amino Acid CompositionsSome Proteins Contain Chemical GroupsOther Than Amino Acids44单纯蛋白质（单纯蛋白质（simple protein）结合蛋白质结合蛋白质 =蛋白质部分蛋白质部分 +非蛋白质部分非蛋白质部分（conjugated protein）辅基辅基（prosthetic group）蛋白质的功能蛋白质的功能 催化（酶）催化（酶）调节调节 运输运输 贮存贮存 运动运动 结构结构 支架支

37、架 保护和攻击保护和攻击45In Summary 氨基酸氨基酸 L-L-氨基酸氨基酸 按按R R基团分类基团分类 兼性离子兼性离子 等电点等电点pIpI 滴定曲线滴定曲线 多肽多肽 肽键肽键 结构结构 大小大小 分类分类Amino acids Peptide Protein Enzyme R group Chiral center Enantiomers(对映体)Disulfide bond（二硫键）Zwitterion（两性离子）Titration curves Isoelectric point(pI)Peptide bond Oligopeptide Oligomeric protein（寡聚蛋白）Prosthetic group（辅基）46Terms