Chapter 5 Part 2

1. Chapter 5 Part 2 Proteins and Nucleic Acids

2. Protein Quick Facts • More than 50% of the dry mass of a cell is comprised of proteins • Polypeptide DOES NOT mean protein! Proteins are 1 or more polypeptides put together • Each protein has a unique 3-D shape that determines its function

3. Proteins • Proteins have many structures, resulting in a wide range of functions • Proteins do most of the work in cells and act as enzymes • Proteins are made of monomers called amino acids

4. Table 5.1 • An overview of protein functions

5. Substrate binds to enzyme. 1 Active site is available for a molecule of substrate, the reactant on which the enzyme acts. 2 2 Substrate (sucrose) Glucose Enzyme (sucrase) OH H2O Fructose H O 4 Products are released. 3 Substrate is converted to products. Figure 5.16 • Enzymes • Are a type of protein that acts as a catalyst, speeding up chemical reactions

6. Enzymes • Are not consumed by reactions (reusable) • Facilitate metabolism • Most structurally sophisticated molecule known

7. Polypeptides • Polypeptides • Are polymers (chains) of amino acids • A protein consists of one or more polypeptides • Polypeptides may form coils and/or folds to create the 3D shape of a protein

8. Amino acids • Are organic molecules possessing both carboxyl and amino groups • Differ in their properties due to differing side chains, called R groups Notice the asymmetric carbon that makes the center – four different pieces are attached 

9. CH3 CH3 CH3 CH CH2 CH3 CH3 H CH3 H3C CH3 CH2 CH O O O O O H3N+ H3N+ H3N+ H3N+ C H3N+ C C C C C C C C C O– O– O– O– O– H H H H H Valine (Val) Leucine (Leu) Isoleucine (Ile) Glycine (Gly) Alanine (Ala) Nonpolar CH3 CH2 S H2C CH2 O NH CH2 H2N C C CH2 CH2 O– CH2 O O O H H3N+ H3N+ C C C C H3N+ C C O– O– O– H H H Phenylalanine (Phe) Proline (Pro) Methionine (Met) Tryptophan (Trp) Figure 5.17 Twenty Amino Acids • 20 different amino acids make up proteins (hydrophobic by nature)

10. OH NH2 O C NH2 O C OH SH CH2 CH3 OH Polar CH2 CH CH2 CH2 CH2 CH2 O O O O O O H3N+ H3N+ H3N+ H3N+ H3N+ H3N+ C C C C C C C C C C C C O– O– O– O– O– O– H H H H H H Glutamine (Gln) Tyrosine (Tyr) Asparagine (Asn) Cysteine (Cys) Serine (Ser) Threonine (Thr) Basic Acidic NH3+ NH2 NH+ O– O –O O CH2 C NH2+ C C NH Electrically charged CH2 CH2 CH2 CH2 CH2 O O H3N+ H3N+ CH2 CH2 C CH2 C C C O O– H3N+ O– CH2 C CH2 C H O H H3N+ O– C C CH2 H O O– H3N+ C C H O– H Lysine (Lys) Histidine (His) Arginine (Arg) Glutamic acid (Glu) Aspartic acid (Asp) (Hydrophillic by nature) (ionized in cells)

11. Amino Acid Facts • 20 amino acids create all the unique polypeptide chains needed by organisms • Physical and chemical differences come from the R-group, also known as a “side chain” • Asymmetric center carbon = alphacarbon

12. Amino Acid Polymers • Amino acids are linked by peptide bonds during a dehydration synthesis reaction

13. Amino Acid Polymers • Many peptide bonds between many amino acids form a polypeptide with an amino end (N-terminus) and a carboxylend (C-terminus) • THEME: Building many complex molecules in a variety of forms from limited building blocks

14. Determining Amino Acid Sequence • Pioneer – Frederick Sanger • Cambridge University, England, 1940s/50s • Used protein digesting enzymes and hydrolysis to break proteins at different points. Used amino acid overlaps in sequences to determine full protein amino acid sequences

15. Protein Conformation and Function • A protein’s specific conformation (shape) determines how it functions • Folding of the protein is spontaneous and driven by bonds between parts of the chain

16. Amino acid subunits +H3NAmino end Pro Thr Gly Gly Thr Gly Glu Seu Lys Cys Pro Leu Met Val Lys Val Leu Asp Ala Arg Val Gly Ser Pro Ala Glu Lle Asp Thr Lys Ser Tyr Trp Lys Ala Leu Gly lle Ser Pro Phe His Glu His Ala Glu Val Thr Phe Val Ala Asn lle Thr Asp Ala Tyr Arg Ser Ala Arg Pro Gly Leu Leu Ser Pro Tyr Ser Tyr Ser Thr Thr Ala o Val c Val Glu – Lys o Thr Pro Asn Carboxyl end Figure 5.20 Four Levels of Protein Structure • Primary structure • Is the unique sequence of amino acids in a polypeptide • Remember: one end will be an amino group and the other a carboxyl group

17. H H H H H H O O O O O O O H H H H H H R R R R R R R C C C C C C C C C C C C C N N N N N N N N N N N N N C C C C C C C C C C C C C C R R R R R R H H H H H H H O O O O O O O H H H H H H H  pleated sheet H O H H Amino acidsubunits C C N N N C C C R H O H H H H H H N N N N N N  helix C C O C H H H C C C R R R R R H H C C C C C C O O O O H C R O C C O H C O N N H C C H R H R Figure 5.20 • Secondary structure • Is the folding or coiling of the polypeptide into a repeating configuration • Includes the  helix and the  pleated sheet

18. Secondary Structure • Coils and folds in the chains of amino acids are the result of hydrogen bonds between non-amino sides of chains. These numerous weak bonds together form a strong supportive network. • Example: Many fibrous proteins have an alpha helix coil at every 4th amino acid

19. Alpha vs. Beta ALPHA BETA 2 or more regions of the polypeptide chain lying side by side connected by H+ bonds between parallel backbones Makes up core of many globular proteins and some fibrous proteins, adding strength • Bonding is not parallel, but takes on the shape of a wavelength • Found in many fibrous proteins • Numerous H+ bonds

20. Hydrophobic interactions and van der Waalsinteractions CH CH2 CH2 H3C CH3 OH Polypeptidebackbone H3C CH3 Hyrdogenbond CH O HO C CH2 CH2 S S CH2 Disulfide bridge O -O C CH2 CH2 NH3+ Ionic bond • Tertiary structure • Is the overall three-dimensional shape of a polypeptide • Results from interactions between amino acids and R groups

21. Tertiary Contributors • Nonpolar side chains group together at center of protein to be away from water – held by van der Waals interactions • H+ bonds between polar side chains and ionic bonds between +/- side chains • Disulfide bridges (S-S bonds)

22. Polypeptidechain Collagen  Chains Iron Heme  Chains Hemoglobin • Quaternary structure • Is the overall protein structure that results from the aggregation of two or more polypeptide subunits

23. +H3N Amino end Amino acid subunits helix Review of Protein Structure

24. Sickle-Cell Disease: A Simple Change in Primary Structure • Sickle-cell disease results from a single amino acid substitution in the protein hemoglobin • Valine is substituted for glutamic acid • RESULT: Molecules that individually transport oxygen instead group to form fibers

25. Normal hemoglobin Sickle-cell hemoglobin Primary structure Primary structure . . . . . . Exposed hydrophobic region Val His Leu Thr Pro Glul Glu Val His Leu Pro Glu Thr Val 5 6 7 3 4 5 6 7 1 2 1 2 3 4 Secondaryand tertiarystructures Secondaryand tertiarystructures  subunit  subunit     Quaternary structure Hemoglobin A Quaternary structure Hemoglobin S     Molecules interact with one another tocrystallize into a fiber, capacity to carry oxygen is greatly reduced. Function Molecules donot associatewith oneanother, eachcarries oxygen. Function 10 m 10 m Normal cells arefull of individualhemoglobinmolecules, eachcarrying oxygen Red bloodcell shape Red bloodcell shape Figure 5.21 Fibers of abnormalhemoglobin deform cell into sickle shape.

26. What Determines Protein Conformation? • Protein conformation depends on the physical and chemical conditions of the protein’s environment • Temperature, pH, etc. affect protein structure

27. Denaturation Normal protein Denatured protein Renaturation Figure 5.22 Denaturation is when a protein unravels and loses its native conformation (shape)

28. Causes and Effects of Denaturation • Protein is transferred from aqueous solution to an organic solvent like ether or chloroform • Result – hydrophillic regions branch outward instead of inward • Other agents can disrupt H+ bonds, ionic bonds, and disulfide bridges

29. Causes and Effects of Denaturation • Excessive heat overpowers weak interactions that stabilize conformation • Examples: Cooking an egg at high heat denatures proteins because the insoluble proteins solidify • Deadly high fevers denature enzymes in the body

30. The Protein-Folding Problem • Most proteins probably go through several intermediate states on their way to a stable conformation (chaperonins like Figure 5.23 assist in this) • Denaturated proteins no longer work in their unfolded condition • Proteins may be denaturated by extreme changes in pH or temperature

31. Correctlyfoldedprotein Polypeptide Cap Hollowcylinder The cap attaches, causing the cylinder to change shape insuch a way that it creates a hydrophilic environment for the folding of the polypeptide. The cap comesoff, and the properlyfolded protein is released. Steps of ChaperoninAction: An unfolded poly- peptide enters the cylinder from one end. Chaperonin(fully assembled) 2 3 1 Figure 5.23 • Chaperonins • Are protein molecules that assist in the proper folding of other proteins

32. X-raydiffraction pattern Photographic film Diffracted X-rays X-ray beam X-raysource Crystal Nucleic acid Protein (b) 3D computer model (a) X-ray diffraction pattern • X-ray crystallography • Is used to determine a protein’s three-dimensional structure Figure 5.24

33. Nucleic Acids • Nucleic acids store and transmit hereditary information • Genes • Are the units of inheritance • Program the amino acid sequence of polypeptides • Are made of nucleotide sequences on DNA

34. The Roles of Nucleic Acids • There are two types of nucleic acids • Deoxyribonucleic acid (DNA) • Ribonucleic acid (RNA)

35. Deoxyribonucleic Acid • DNA • Stores information for the synthesis of specific proteins • Found in the nucleus of cells • Double-stranded structure (double helix) • Contains sugar deoxyribose (lacks an oxygen on the second carbon in its ring)

36. DNA 1 Synthesis of mRNA in the nucleus mRNA NUCLEUS CYTOPLASM mRNA 2 Movement of mRNA into cytoplasm via nuclear pore Ribosome 3 Synthesis of protein Aminoacids Polypeptide Figure 5.25 DNA Functions • Directs RNA synthesis (transcription) • Directs protein synthesis through RNA (translation) • Transmits genes to new cells and/ or offspring

37. Ribonucleic Acid • mRNA directs specific polypeptide formation while working in tandem with ribosomes and tRNA • Contains the sugar ribose • Single stranded

38. 5’ end 5’C O 3’C O O 5’C O 3’C 3’ end OH Figure 5.26 The Structure of Nucleic Acids • Nucleic acids • Exist as polynucleotides (a) Polynucleotide, or nucleic acid

39. Nucleoside Nitrogenous base O 5’C O O CH2 P O O Phosphate group 3’C Pentose sugar Figure 5.26 (b) Nucleotide • Each polynucleotide • Consists of monomers called nucleotides • Sugar + phosphate + nitrogen base

40. Nitrogenous bases Pyrimidines NH2 O O C C CH3 C N CH HN C CH HN CH CH C CH C C CH CH N N O N O O H H H Cytosine C Uracil (in RNA) U Thymine (in DNA) T Uracil (in RNA) U Purines O NH2 C C N N C C NH N HC HC C CH C N N NH2 N N H H Adenine A Guanine G Pentose sugars 5” 5” OH OH HOCH2 HOCH2 O O H H H H 1’ 1’ 4’ 4’ H H H H 3’ 2’ 3’ 2’ H OH OH OH Deoxyribose (in DNA) Ribose (in RNA) Ribose (in RNA) Nucleotide Monomers • Nucleotide monomers • Are made up of nucleosides (sugar + base) and phosphate groups Figure 5.26 (c) Nucleoside components

41. Nucleotide Polymers • Nucleotide polymers • Are made up of nucleotides linked by the–OH group on the 3´ carbon of one nucleotide and the phosphate on the 5´ carbon on the next

42. Gene • The sequence of bases along a nucleotide polymer • Is unique for each gene • Thousands of genes may be held on one strand of DNA

43. The DNA Double Helix • Cellular DNA molecules • Have two polynucleotides that spiral around an imaginary axis • Form a double helix

44. 3’ end 5’ end Sugar-phosphatebackbone Base pair (joined byhydrogen bonding) Old strands Nucleotideabout to be added to a new strand 3’ end A 5’ end Newstrands 3’ end 3’ end 5’ end Figure 5.27 • The DNA double helix • Consists of two antiparallellnucleotide strands • 5’ to 3’ = Building direction

45. A,T,C,G • The nitrogenous bases in DNA • Form hydrogen bonds in a complementary fashion (A with T only, and C with G only)

46. DNA and Proteins as Tape Measures of Evolution • Molecular comparisons • Help biologists sort out the evolutionary connections among species

47. The Theme of Emergent Properties in the Chemistry of Life: A Review • Higher levels of organization • Result in the emergence of new properties • Organization • Is the key to the chemistry of life