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Proteins

Proteins. What is a protein?. A protein is a molecule consisting of amino acids linked in a linear chain through peptide bonds. Protein primary structure. Peptide formation. There are many kinds of proteins. Structural--determine shape and function of cells

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Proteins

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  1. Proteins

  2. What is a protein? • A protein is a molecule consisting of amino acids linked in a linear chain through peptide bonds.

  3. Protein primary structure

  4. Peptide formation

  5. There are many kinds of proteins. • Structural--determine shape and function of cells • Enzymes--speed up chemical reactions • Ligand-binding--bind small molecules and transport them to other locations

  6. Cells • muscle • nerve

  7. Structural proteins • collagen -- in connective tissue such as cartilage • elastin -- in connective tissue such as cartilage • keratin--in hair and nails • actin -- in muscle • myosin -- in muscle to generate mechanical forces

  8. Enzymes • glucose isomerase--convert glucose into fructose • rennin--make cheese • cellulase--break down cellulose into sugars to make ethanol • amylase--detergent for machine dish washing

  9. Ligand-binding proteins. • hemoglobin--transport oxygen from the lungs • antibodies--bind foreign substances for destruction

  10. The string of amino acids tends to “fold” into a shape.

  11. Hemoglobin structure

  12. Heart of Steel (Hemoglobin) by Julian Voss-Andreae

  13. Protein views (Triose phosphate isomerase)

  14. Visualizing proteins

  15. Amino acids • There are 20 different standard amino acids • The different amino acids differ in chemical properties.

  16. Amino Acid 3-Letter 1-Letter Polarity Acidity Hydrophobicity index • Alanine Ala A nonpolar neutral 1.8 • Arginine Arg R polar basic (s) -4.5 • Asparagine Asn N polar neutral -3.5 • Aspartic acid Asp D polar acidic -3.5 • Cysteine Cys C nonpolar neutral 2.5 • Glutamic acid Glu E polar acidic -3.5 • Glutamine Gln Q polar neutral -3.5 • Glycine Gly G nonpolar neutral -0.4 • Histidine His H polar basic (w) -3.2 • Isoleucine Ile I nonpolar neutral 4.5 • Leucine Leu L nonpolar neutral 3.8 • Lysine Lys K polar basic -3.9 • Methionine Met M nonpolar neutral 1.9 • Phenylalanine Phe F nonpolar neutral 2.8 • Proline Pro P nonpolar neutral -1.6 • Serine Ser S polar neutral -0.8 • Threonine Thr T polar neutral -0.7 • Tryptophan Trp W nonpolar neutral -0.9 • Tyrosine Tyr Y polar neutral -1.3 • Valine Val V nonpolar neutral 4.2

  17. Hydrophobicity index. • The larger the index, the stronger the tendency to be internal in the protein; the lower the index, the stronger the tendency to appear near the protein surface. • Amino acids with high index are called hydrophobic; with low index are called hydrophilic.

  18. What is the shape of the protein? • This is the “protein folding problem.” • The geometry and chemistry of the parts of the protein determine how it behaves in the cell.

  19. DNA • DNA is deoxyribose nucleic acid. • It occurs as long molecules in a double helix.

  20. DNA is a long molecule in a double helix

  21. What makes DNA? • DNA consists of sequences of nucleotides. • There are 4 kinds of nucleotide: • Adenine (A), Cytosine (C), Guanine (G), and Thymine (T)

  22. Matching • Each A has weak (“hydrogen”) bonds with T on the other chain. • Each C has weak (“hydrogen”) bonds with G on the other chain.

  23. A single chain carries the information • For example, the two strings might be ACGGTCAG TGCCAGTC • Hence all the information is in the order of A, C, G, T in one of the chains. • We write DNA as a (long) string of A, C, G, T for example AGGCTACATAG…

  24. Human DNA • Humans have 46 chromosomes. • Each chromosome is essentially a double helix of DNA, with variable numbers of nucleotides, from 50,000,000 to 250,000,000 base pairs. • There are a total of about 2,860,000,000 nucleotide pairs.

  25. Genes • A gene is a portion of the DNA that tells how to make a protein.

  26. DNA for beta hemoglobin • ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

  27. Amino Acid 3-Letter 1-Letter Polarity Acidity Hydrophobicity index • Alanine Ala A nonpolar neutral 1.8 • Arginine Arg R polar basic (s) -4.5 • Asparagine Asn N polar neutral -3.5 • Aspartic acid Asp D polar acidic -3.5 • Cysteine Cys C nonpolar neutral 2.5 • Glutamic acid Glu E polar acidic -3.5 • Glutamine Gln Q polar neutral -3.5 • Glycine Gly G nonpolar neutral -0.4 • Histidine His H polar basic (w) -3.2 • Isoleucine Ile I nonpolar neutral 4.5 • Leucine Leu L nonpolar neutral 3.8 • Lysine Lys K polar basic -3.9 • Methionine Met M nonpolar neutral 1.9 • Phenylalanine Phe F nonpolar neutral 2.8 • Proline Pro P nonpolar neutral -1.6 • Serine Ser S polar neutral -0.8 • Threonine Thr T polar neutral -0.7 • Tryptophan Trp W nonpolar neutral -0.9 • Tyrosine Tyr Y polar neutral -1.3 • Valine Val V nonpolar neutral 4.2

  28. DNA determines the order of amino acids • ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

  29. Primary structure for beta hemoglobin--the order • MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

  30. Hemoglobin structure

  31. How does DNA determine the order of amino acids? • Three successive nucleotides form a “codon.” • Different codons stand for different amino acids.

  32. Translating codons • Ala/A GCT, GCC, GCA, GCG Leu/L TTA, TTG, CTT, CTC, CTA, CTG • Arg/R CGT, CGC, CGA, CGG, AGA, AGG Lys/K AAA, AAG • Asn/N AAT, AAC Met/M ATG • Asp/D GAT, GAC Phe/F TTT, TTC • Cys/C TGT, TGC Pro/P CCT, CCC, CCA, CCG • Gln/Q CAA, CAG Ser/S TCT, TCC, TCA, TCG, AGT, AGC • Glu/E GAA, GAG Thr/T ACT, ACC, ACA, ACG • Gly/G GGT, GGC, GGA, GGG Trp/W TGG • His/H CAT, CAC Tyr/Y TAT, TAC • Ile/I ATT, ATC, ATA Val/V GTT, GTC, GTA, GTG • START ATG STOP TAG, TGA, TAA

  33. DNA for beta hemoglobin • ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

  34. Primary structure for beta hemoglobin • MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

  35. Hemoglobin structure

  36. The order of amino acids is important • Consider what may happen when the “wrong” amino acid is in a certain position.

  37. Primary structure for beta hemoglobin • MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

  38. Sickle cell anemia beta hemoglobin • MVHLTPVEKSAVTALWGKVNVDEVGGEALGRLLVVYWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

  39. Amino Acid 3-Letter 1-Letter Polarity Acidity Hydrophobicity index • Alanine Ala A nonpolar neutral 1.8 • Arginine Arg R polar basic (s) -4.5 • Asparagine Asn N polar neutral -3.5 • Aspartic acid Asp D polar acidic -3.5 • Cysteine Cys C nonpolar neutral 2.5 • Glutamic acid Glu E polar acidic -3.5 • Glutamine Gln Q polar neutral -3.5 • Glycine Gly G nonpolar neutral -0.4 • Histidine His H polar basic (w) -3.2 • Isoleucine Ile I nonpolar neutral 4.5 • Leucine Leu L nonpolar neutral 3.8 • Lysine Lys K polar basic -3.9 • Methionine Met M nonpolar neutral 1.9 • Phenylalanine Phe F nonpolar neutral 2.8 • Proline Pro P nonpolar neutral -1.6 • Serine Ser S polar neutral -0.8 • Threonine Thr T polar neutral -0.7 • Tryptophan Trp W nonpolar neutral -0.9 • Tyrosine Tyr Y polar neutral -1.3 • Valine Val V nonpolar neutral 4.2

  40. Simple model • Pretend there are only 2 kinds of amino acid--H and P. • H stands for “hydrophobic”. • Pretend that they must be placed on a grid. • Example: HHPPPPPPPHH

  41. A folding of HHPPPPPPPHH

  42. Another folding of HHPPPPPPPHH

  43. Energy • HH has energy -1. • PP has energy 0. • HP has energy 0. • PH has energy 0. • The protein folds so as to minimize the energy.

  44. A folding of HHPPPPPPPHH with energy -2

  45. A folding of HHPPPPPPPHH with energy -4

  46. A folding of HHPPPPPPPHH with ? energy

  47. The real problem • There are 20 amino acids. • Pairs have different energies. • Typically a protein has about 100 amino acids. • The protein is in 3 dimensions. • It does not need to be on a grid. • It must be worked on a computer.

  48. The Direct Approach • Write down a formula for the energy E, taking into account the (variable) locations of all amino acids, all charges and electrostatic attractions and repulsions, and all constraints. • Minimize E.

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