Chemical components of cells 1. Chemical bonds 2. Water and hydrogen bonds 3. Macromolecules: polysaccharides, proteins and nucleic acids

Transcription

1 Chemical components of cells 1. Chemical bonds 2. Water and hydrogen bonds 3. Macromolecules: polysaccharides, proteins and nucleic acids Protein structure and function 1. Different levels of protein structures 2. α-helix and β-sheets 3. Methods to seperate and analyse proteins; from biochemistry to proteomics

2 Covalent bonds are characterized by particular geometries

3 Length and strength of chemical bonds

4 C=C double bonds are shorter and more rigid than C-C single bonds

5 Polar and nonpolar covalent bonds polar e.g. O-H, -N-H nonpolar e.g. -C-H

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9 Hydrophobic forces

10 4 main families of organic molecules in cells

11 Macromolecules in cells

12 Macromolecules are made from monomeric subunits

13 Macromolecules are formed by adding subunits to one end (via condensation reactions) -> specific sequence of subunits

14 Condensation and hyrdrolysis

15 Polysaccharides

16 Structural polysaccarides Cellulose, cotton (glucose) Chitin (N-acetylglucosamine) Glycosaminoglycans, heparin

17 Protein structure and function

18 Amino acids, the subunits of proteins

19 Proteins consist of L-amino acids

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21 Peptide bonds are rigid, planar units

22 The 20 amino acids found in proteins

23 The 4 levels of protein structure Primary structure Secondary structure Tertiary structure Quartiary structure

24 Polypeptide backbone and side chains

25 Noncovalent bonds specify the precise shape of a macromolecule

26 Noncovalent bonds fold proteins

27 Proteins fold into compact conformations Hydrophobic forces cluster hydrophobic side chains in the interior of the folded protein Polar side chains tend to arrange themselfes near the outside of the folded protein > hydrogen bonds with water

28 Hydrophilic (green) and hydrophobic (red) amino acid residues in a soluble protein Cytochrom c

29 H-bonds within a protein molecule

30 Disulfide bonds can help to stabilize a favored protein conformation S-S bonds are only found in extracellular proteins

31 Elastin polypeptide chains form crosslinked rubber-like elastic fibers

32 Insulin The hormone insulin was the first polypeptide for which the complete amino acid sequence could be determined.

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34 The α-helix

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36 A α-helix can cross a lipid bilayer Note: An α-helix is no channel! The space is occupied by the peptide backbone. To make a channel through a membrane, other (bigger) structures are required.

37 Long, rodlike coiled-coil structures Examples: α-keratin in skin, myosin in muscles

38 The β-sheet

39 Parallel and antiparallel β-sheets N-terminus C-terminus

40 Many proteins are folded into seperate functional domains camp-binding domain CAP (catabolite activator protein) DNA-binding domain

41 Protein domains and protein families

42 X-ray crystallography

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44 Proteins are dynamic structures RuBisCO (Ribulose-1,5- bisphosphatcarboxylase) is the most abundant protein on Earth (in plant leaves); 10 kg per person on earth. RuBisCO catalyzes the first major step of carbon fixation.

45 Hemoglobin is formed as symetrical assembly of two different subunits

46 Jacob, Monod and Changeux discovered the regulatory importance of allosteric changes in the conformation of many enzymes

47 Proteins can bind to one another trough compementary charges on their surfaces

48 Proteins can pack to form a filament, a tube, or a spherical shell

49 The ribosome, a complex of about 90 macromolecules (RNA and proteins)

50 Structure of a spherical virus

51 The protein binding site is highly selective

52 Enzyme catalysis

53 Regulation of protein activity by phosphorylation The addition of a single phophate group with two negative charges can dramatically change the conformation of a protein

54 Methods used in protein chemistry

55 Homogentization

56 Centrifugation

57 Differential Centrifugation

58 Column chromatography

59 Different kinds of chromatography

60 Gel electrophoresis

61 IE and 2D-SDS-PAGE

62 Identification of proteins by mass spectroscopy

63 Genomics & Proteomics

64 Protein chips: Global analysis of protein activities

65 Nucleotides, subunits of DNA and RNA ATP nucleoside nucleotide

66 ATP is the energy carrier in cells

67 DNA

68 The DNA-helix In 1953, based on X-ray diffraction images taken by Rosalind Franklin and the information that the bases were paired, James D. Watson and Francis Crick suggested the DNA structure in the journal Nature. Experimental evidence for Watson and Crick's model were published in a series of five articles in the same issue of Nature.

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71 Genomics Genome sizes of different organisms are very different

72 Important genome sequencing papers Mouse Nature. 420: (5 December 2002) Human Nature. 409: (15 February 2001) Arabidopsis - First Plant Sequenced Nature 408: (14 December 2000) Fruit Fly Science. (24 March 2000) 287: Roundworm C. elegans - First Mutlicellular Eukaryote Sequenced Science. (11 December 1998) 282: Bacteria - E. coli Science. 277: (5 September 1997) Yeast Science. (25 October 1996) 274: 546, Bacteria - H. influenzae - First Free-living Organism to be Sequenced Science. (28 July 1995) 269:

73 There are more than 600 genomes completey sequenced in 2007 See GOLD (genome online databases at

74 Genome sizes and gene numbers organism estimated size gene number average gene density Chromo -somes Homo sapiens (human) Rattus norvegicus (rat) Mus musculus (mouse) Drosophila melanogaster (fruit fly) Arabidopsis thaliana (plant) Caenorhabditis elegans (roundworm) Saccharomyces cerevisiae (yeast) Escherichia coli (bacteria) H. influenzae (bacteria) 2900 million bases ~30,000 1 gene per 100,000 bases 46 2,750 million bases ~30,000 1 gene per 100,000 bases million bases ~30,000 1 gene per 100,000 bases million bases 13,600 1 gene per 9,000 bases million bases 25,500 1 gene per 4000 bases 5 97 million bases 19,100 1 gene per 5000 bases 6 12 million bases gene per 2000 bases million bases gene per 1400 bases million bases gene per 1000 bases 1 Genome size does not correlate with evolutionary status, nor is the number of genes proportionate with genome size.

75 The future of DNA sequencing In May 2007, James D. Watson, the co-discoverer of the molecular structure of DNA, became the first person to receive his own complete personal genome sequenced. The cost was less than $1 million (0.03 cents per base). It took less than two months. It is realistic to expect that within the next ten years, rapid low-cost sequencing of human genomes will become a reality. Pharmacogenomics Genotyping