生物化学教学课件：peptidebond

1、Proteins220 common amino acids3D-, L- stereoisomers （立体异构体）Optical absorbance （光吸收）pI (isoelectric point) （等电点）Other amino acids and post-translational modifications（翻译后修饰）Something to know about amino acids 4Only the L-form of amino acids are used to build proteins.Amino acids, except glycine, are

2、chiral（手性的）.5678(Lambert-Beer law)Optical absorbance（光吸收）9OD280 for protein quantification10A few examples of other amino acids11Peptide bond 肽键12Ser-Gly-Tyr-Ala-LeuLeu-Ala-Tyr-Gly-SerMain chain（主链） vs. side chain （侧链）SGYALLAYGS13Amino acid vs. residue (残基).OHH1415Some small peptides of physiologica

3、l interestAspartame: methyl ester derivative of L-Aspartyl-L-phenylalanine; 200 x sweeter than sugar.16Some small peptides of physiological interestGlutathione (GSH)（谷胱甘肽）: tripeptide scavenger of oxidizing agents; oxidized form consists of two glutathione molecules joined by disulfide bridge.17insu

4、lin胰岛素18Frederick Sanger The Nobel Prize in Chemistry 1980 The Nobel Prize in Chemistry 1958 for his work on the structure of proteins, especially that of insulinfor their contributions concerning the determination of base sequences in nucleic acids 19Nobel Prize in Chemistry 1964 for her determinat

5、ions by X-ray techniques of the structures of important biochemical substances.Dorothy Crowfoot Hodgkin Insulin structure 2021Number of negatively charged residues (Asp + Glu): 9Number of positively charged residues (Arg + Lys): 17Lysozyme 溶菌酶Primary sequence of 129 residues:KVFGRCELAAAMKRHGLDNYRGYS

6、LGNWVCAAKFESNFNTQATNRNTDGSTDYGILQINSRWWCNDGRTPGSRNLCNIPCSALLSSDITASVNCAKKIVSDGNGMNAWVAWRNRCKGTDVQAWIRGCRLTheoretical pI: 9.32 (http:/cgi-bin/protparam/protparam)22a-helixb-sheetLysozyme structure (PDB 3LYM)23An a-helix in lysozyme: RCELAAAMKRH (color code: CNO)The a helixTo make optimal use of inter

7、nal hydrogen bonds.Every helical turn extends about 5.4 along the axis. Only right-handed helix.Every helical turn includes 3.6 residues, so that every residue turns 100 degrees.245.4 25Interaction between side chains of residue i and i+3 or i+4;Pro rarely appears in a-helix .An a-helix in lysozyme:

8、 RCELAAAMKRH 9026Linus Pauling (1901-1994) got the Nobel Prize in Chemistry in 1954 “for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances”.27Coiled-coil structure(Myosin II coiled-coil, PDB 2FXO)90 Heptad repeats in seque

9、nce: -(abcdefg)n-a,d: hydropholic; e,g: charged. 28 abcdefg-MASMKEE FTRLKEA LEKSEAR-Example: coiled-coil from myosin II (PDB 2FXO)-MASMKEEFTRLKEALEKSEAR-(Myosin II coiled-coil, PDB 2FXO)29a-helixb-sheetLysozyme structure (PDB 3LYM)30b-sheet31The b sheets3233Extremely colorful protein structures34imm

10、unoglobulin domain 免疫球蛋白结构域PDB: 1IGT35Protein quaternary structures3637Denaturation of proteinsA loss of three-dimensional structure sufficient to cause loss of function. (/biotech/resources/proteins/labManual/images/220_04_021.gif)38Most proteins can be denatured by heatMedical sterilization.An exc

11、eption is the thermophilic bacteria.39Chaotropic reagents disturb the hydrogen bond network in proteins. O NH2 C NH2 NH2+ Cl- NH2 C NH2Urea 尿素Guanidine hydrochloride (GdnHCl) 盐酸胍401929年在波士顿召开的第13届国际生理学会上他提出蛋白质变性学说：认为天然蛋白质分子不是一长的直链而是一紧密的结构；这种结构是借肽键之外的其他键，将肽链的不同部分连接而形成的，所以容易被物理及化学的力所破坏，即从有规则的折叠排列形式变成不

12、规则及松散的形式。这个学说对于研究蛋白质大分子的高级结构有重要价值。 吴宪 (18931959)41Protein sequence determines its tertiary structure.The Nobel Prize in Chemistry 1972 for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation”.Christian B. Anfinsen This is true for only a small number of proteins.42Misfolding diseases/images/figure1.gifPrion diseases: mad cow disease (bovine spongiform encephalopathy, BSE), Cr