1、DateChapterLecturerMar. 3Chapter 1-2 Foundations of Biochemistry, waterDr. Chang Mar. 10 Chapter 3. Amino acids, peptides and proteins Dr. SuMar. 18*Chapter 3 Amino acids, peptides and proteins Dr. SuMar. 24*Chapter 4 The three-dimensional structures of protein Dr. SuMar. 31Chapter 4 The three-dimen

2、sional structures of protein Dr. SuApr. 7Chapter 5 Protein FunctionDr. ChangApr. 14Chapter 5 Protein FunctionDr. Chang Apr. 21Chapter 6 EnzymesDr. ChangApr. 28Chapter 6 EnzymesChapter 8 Nucleotides and nucleic acids Dr. ChangMay 12Dr. KongMay 19Chapter 9 DNA-based information technoloogiesDr. KongMa

3、y 26Chapter 7 Carbohydrates and Glycobiology Dr. QinJune 2Chapter 10 Lipid Dr. QinJun. 9Chapter 11 Biological membranes and tansport Dr. QinJun. 16Chapter 12 Biosignaling Dr. QinTeaching arrangements for Biochemistry I 2007(Drs. Zengyi Chang, Xiaodong Su, Daochun Kong, Yongmei Qin) Saturdays, 8:00 -

4、 11:00AM; 電教112 Chapter 3 pp 75-115 Amino Acids, Peptides and Proteins 氨基酸、肽及蛋白質(zhì)Nelson, D. L., and Cox, M. M. (2005) Lehninger Principles of Biochemistry, 4th edition. Biochemistry asks how the remarkable properties of living organisms arise from the thousands of different lifeless biomolecules. Whe

5、n these molecules are isolated and examined individually, they conform to all the physical and chemical laws that describe the behavior of inanimate matteras do all the processes occurring in living organisms. The study of biochemistry shows how the collections of inanimate molecules that constitute

6、 living organisms interact to maintain and perpetuate life animated solely by the physical and chemical laws that govern the nonliving universe.ATPFrom Petras P. Dzeja and Andre Terzic The Journal of Experimental Biology 206, 2039-2047 (2003)DG = DH - TDSWhat is protein?Components of organisms:Enzym

7、es (metabolism)Transport (O2, membrane )Movements (muscles)Antibodies (immunity )Brain Protections (horns, skins)YearInterweaving of the historical traditions of biochemistry, cell biology, and genetics.Proteins were thought to carry genetic information182818971944Miescher discovered DNAThe Nobel Pr

8、ize in Physiology or Medicine 1953 for his discovery of the citric acid cycleHans Adolf Krebs (1900-1981)Sheffield University, Sheffield, United Kingdom The research I have been doing - studying how foodstuffs yield energy in living cells - does not lead to the kind of knowledge that can be expected

9、 to give immediate practical benefits to mankind. I have chosen this field of study, it was because I believed in its importance in spite of its theoretical character. My reason for this belief was that all living things must be continuously fed with energy and I am convinced that an understanding o

10、f the process of energy production will eventually help us in solving some of the practical problems of medicine. Nobel Banquet Speech, Dec. 1953The Nobel Prize in Physiology or Medicine 1962for their discoveries concerning the molecular structure of nucleic acids and its significance for informatio

11、n transfer in living material Francis H. C. Crick Maurice H. F. Wilkins James D. Watson The central dogma 中心法則Flow of information in gene expressionEveryday homework for biologists Evolution！Metabolism 新成代謝合成代謝分解代謝Metabolism Pathways or NetworksCommon Structural Featuresa carboxyl group(羧基)an amino

12、group（氨基）side chains, or R groupsWhen the R group contains additional carbons in a chain, they are designated , , , etc., proceeding out from the a carbon.RThe classifies of standard amino acidsbased on R groupFive main classes of amino acids:nonpolar and aliphaticaromatic (generally nonpolar)polar

13、but unchargednegatively chargedpositively charged3.1.3 Nonstandard amino acids 4羥(基)脯氨酸5羥(基)賴氨酸硒代半胱氨酸鏈霉素6N甲基賴氨酸 羥基谷氨酸鳥氨酸瓜氨酸About 300 kinds of a. a. not occurring in proteins Selenocysteine - the 21st amino acidSeCaCbHHHSecThe occurrence of Selenocysteine (Sec) was first demonstrated for protein A of

14、 glycine reductase Cone et al. 1976Sec is used in the active site of some redox enzymes:formate dehydrogenase glutathione peroxidase iodothyronine 5-deiodinaseThe only genetically coded non-standard amino acid硒代半胱氨酸Prokaryotic selenocysteine incorporation4 genes are essential:SelA selenocysteine syn

15、thaseSelB elongation factor SelBSelC tRNASecSelD seleno- phosphate synthaseSelCO-C-C-CH2-OHINH2H l Seryl tRNA synthetaseSelBGTPSelenocysteineUGASelenoprotein mRNAO-C-C-CH2-Se-INH2H ISelASelenideSelenomono-phosphateSelDATP22nd AMINO ACID IDENTIFIED in 2002Methanogen uses stop codonto genetically enco

16、de l-pyrrolysineScience, 296, 1459 and 1462 (2002). Amino Acids -Acids and BasesZwitterion(兩性離子)Nonionic and zwitterionic forms of amino acids兩性離子形式非離子形式Characteristic titration curves of amino acids Effect of the chemical environment on pKaTitration curve for glutamateTitration curve for histidine

17、Peptides and proteinsPeptide bond formation by CONDENSATION 縮水反應(yīng)The structure of a pentapeptide(五肽)Proteins And Prosthetic groups (輔基)Levels of structure in proteinsEveryday homework for biologists Evolution！Protein sequences and Evolution！Introduction to Bioinformatics:Sequence alignment; Homologs;

18、Paralogs; orthologs;Blosum (blocks substitution matrix) ; Signature sequences; Current phylogeny tree of life (by Carl Woese) Working with proteinsMethods for separating proteins take advantage of properties such as charge, size, and solubility, which vary from one protein to the next. Because many

19、proteins bind to other biomolecules, proteins can also be separated on the basis of their binding properties. 1. Proteins can be separated and purified James B. Sumner Cornell Medical SchoolFdd 1887Nobelpris 1946Lyckades mot allas frvntningar rena och kristallisera ett enzym, ureas 1926. Proteiner m

20、ste ha en vlordnad struktur!John H. Northrop Columbia universityFdd 1891Nobelpris 1946Isolerade och kristalliserade bl a pepsin (1929)蛋白質(zhì)可以通過各種生物化學(xué)技術(shù)純化利用蛋白質(zhì)的溶解度、凈電荷、大小以及與配體結(jié)合特異性上的微小差異。有透析、凝膠過濾、離子交換層析、親和層析、電泳（垂直板電泳、等電聚焦電泳、雙向電泳）等分離純化方法。透析Salting out and dialysis(透析)Column chromatography Ion-exchange c

21、hromatography Size-exclusion chromatography Affinity chromatography . . . . . .Ion-exchange Chromatography離子交換 分離氨基酸常用的是帶有耐酸性非常強的磺酸根SO3Na（以鹽的形式出現(xiàn)）的強陽離子交換樹脂。首先將這種樹脂填充到柱子中，然后注入含有樣品的流動相，樣品中含有陽離子成分X，通過靜電吸引，與樹脂中的帶電基團(tuán)相互作用，結(jié)果X與Na交換，即發(fā)生陽離子交換后，形成SO3X。Size-exclusion Chromatography 分子篩This method separates proteins according to size. The column contains a cross-linked polymer with pores of selected size. Larger proteins m