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Biochemistry Chapter 6

Biochemistry Chapter 6

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Biochemistry Chapter 6

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  1. BiochemistryChapter 6 The Three-Dimensional Structure of Proteins Mak Oi Tong

  2. Introduction This chapter is devoted to an examination of: • the several levels of protein structure – their geometry • how they are stabilized and • their importance in protein function.

  3. Structure of proteins • Primary structure : the amino acid sequence of protein molecules. • Secondary structure : the local regular folding (direction) of protein molecules. • Tertiary structure : the final 3-dimensional (folded) form of protein molecules. • Quaternary structure : the arrangement of several polypeptide chains (subunits). • Conformation and configuration.

  4. Secondary StructureRegular Ways to Fold the Polypeptide Chain Discovery of Regular Polypeptide Structures (Figure 5.12b, Figure 6.2, Figure 6.3, Figure 6.4) • Bond lengths and bond angles should be distorted (changed) as little as possible shown in Fig. 5.12b. • No two atoms should approach one another more closely than is allowed by their van der Waals radius. • The amide group must remain planer and in the trans configuration. • Hydrogen bonds are most probably used to stabilize the peptide folding between amide protons and carbonyl oxygen.

  5. Fig. 6.2

  6. Molecular Helices and Pleated Sheets • (Figure 6.5, Figure 6.6, Table 6.1)

  7. α-Helix • Only right-handed helix found. • Hydrogen bonds are found between the amide hydrogen and carbonyl oxygen. • A loop of 13 atoms is formed between the hydrogen bond. • 3.6 amino acids per turn of helix. • The repeat (c) is 18 amino acid residues. • The (p), distance per turn, is 0.54 nm, and the rise, distance between each atom is 0.15 (0.54/3.6). • α-Helix is also called 3.613 helix, compared to π-helix 4.416 and 310 helix. • Proline is the α-breaker.

  8. Fig. 6.3

  9. Fig. 6.4

  10. Fig. 6.5

  11. Fig. 6.6

  12. β-sheet (pleated sheet) • Two types of β-sheet, parallel (same N to C direction) and anti-parallel (opposite N to C direction) between polypeptide chains. • β-Sheet contains 2 amino acid residues per turn, and cannot form hydrogen bond between amide hydrogen and carboxyl oxygen. • Hydrogen bonds can only formed between adjacent polypeptide chains. • Anti-parallel form is more stable than parallel form.

  13. Ramachandran Plots(Figure 6.2, Figure 6.8, Figure 6.9, Figure 6.10) • A map (Fig. 6.8) describes the backbone conformation of any particular residue in a protein corresponding to the angle Φ (phi) and Ψ (psi) • Rotation of the corresponding angle Φ and Ψ are given by the arrow in clockwise for +180° when looking in either direction from the α-carbon. • This is called Ramachandran plot after the biochemist who first found it. • If all AA residues in a protein have the same secondary structure (e.g. α-helix), the points for all residues would superimpose (come together at one single point).

  14. Because of the steric effect and van der Waals radii, only a relatively small fraction of conformations is possible, the uncolored areas of the plot in Fig. 6.8. • Only right-hand helix is favoured because all AAs are L-form. • Some points of proteins will fall in the non-allowed regions because of the glycine residue. • The conformation Φ = 0, Ψ = 0 is not allowed in any polypeptide chain because of the steric clash between the carbonyl oxygen and amino proton.

  15. Fig. 6.8

  16. Fig. 6.9

  17. Fig. 6.10

  18. Fibrous Proteins Structural Materials of Cells and Tissues (Table 6.2) • More than 1/3 or more of the body protein in large vertebrates. • Functions include: • External protection such as skin, hair, feather and nail. • Structure and support, shape and form, tendons, cartilage and bone. • Native conformations of fibrous proteins are stable proteins after isolated and will not be denatured or unfolded.

  19. Keratins • Two classes of keratin, α- and β-keratins. • α- Keratins is the major fibrous proteins of hair and wool. • Each α-keratin molecule contains over 300 residues in length and all are α-helical. • Two α-keratin helices bond together by their hydrophobic R-side groups. • The higher amounts of AAs are serine, glutamine, glutamic acid and cysteine. • Disulfide cross-links are found in nail and hair (fewer), and human hair for permanent wave.

  20. Fig. 6.11

  21. β-Keratin • Contains β-sheet structure. • Are found mostly in birds and reptiles for feather and scales.

  22. Fibroin • They areall anti-parallel pleated sheet structure. • Comprise almostglycine, alanineand serine AA. Gly-ala-gly-ala-gly-serine-gly-ala-ala- gly- This alternation allows the β-sheet to fit together. • The structure is strong and inextensible. • No intrachain hydrogen bond, only interchain hydrogen bonds. • No cystine cross-linkage presence. • The fibers are very flexible, e.g. silk.

  23. Fig. 6.12

  24. Collagen (Figure 6.13) • Collagen is about one third of total protein in large animals, and is the major constituent of tendons and skin. • Basic unit is tropocollagen which consists of three polypeptide chains in left-handed helix tightly coiled into a three-strand rope in right-handed helix, arranged in head to tail. • Tropocollagen have total about 3000 AA residues (each polypeptide has 1000 AA residues), having of molecule weight of 300,000. • Every third residue can be only glycine because of the bulky effect.

  25. Fig. 6.13

  26. Proline or 4-hydroxyproline is found in tropocollagen molecule, and a repetitive sequence is present of the form gly-X-Y, where X is often proline and Y is proline or hydroxyproline. • Hydrogen bonds are present among the polypeptides of tropocollagen. • Vitamin C is required for the enzyme to catalyze the hydroxylation of proline to hydroxyproline. • Scurvy, a disease which is the weakening of collagen fibers caused by the failure to hydroxylate proline, is a symptom of extreme vitamin C deficiency.

  27. Collagen cannot be stretched. • The toughness of collagen is due to the cross-linking of tropocollagen molecules to one another by a reaction involving lysine side chains. • This process continues through life, and the accumulation cross-links make the collagen steadily less elastic and more brittle, the signs of aging.

  28. Collagen Synthesis (Figure 6.14) • Posttraslational modification is present in the collagen synthesis. • Procollagen is yield having about 1500 residues of which 500 are in N- and C-terminals regions that do not have the typical collagen fiber sequence. • The procollagen triplexes are exported into the extracellular space and the N- and C-terminals regions are cleaved off by specific proteases. • See Fig. 6.14 for further discussion.

  29. Fig. 6.14

  30. Elastin • Basic component of connective tissue of blood arteries and ligaments. • Structure is similar to collagen. • The basic unit of elastin fibrils is tropoelastin. • It contains rich in glycine and alanine, and also high % of lysine but fewer of proline. • The ability for stretch in elastin is caused by the special structure of desmosine cross-linked by four lysine residues to become a form of highly interconnected, rubbery network.

  31. Globular Proteins: Tertiary Structure and Functional Diversity

  32. Different Folding for Different Functions (Figure 6.1, 6.15 and 6.16) • Globular proteins which are named because their polypeptide chains are folded into compact structures. • They are the important structures for all kinds of enzymes, hormones and other functional proteins. • Their tightly folded conformations are referred as the tertiary structure and are the crucial factor for the biological functions. • Many globular proteins carry prosthetic groups, the non-amino acid small molecules that may be noncovalently or covalently bonded to the proteins to fulfill special functions. • Every globular protein has a unique tertiary structure that is made up of secondary structure elements such as helics, β -sheet.

  33. Varieties of Globular Protein Structure: Patterns of Folding Figure 6.16, 6.17, 6.18, and 6.19) • Although there will be infinite number of globular protein folding, some principles of protein folding are found. • Many proteins are made up of a number of domains, a compact locally folded region of tertiary structure, which perform different functions of proteins. • Two major kinds of folding patterns, α-helic and β-sheet.

  34. Fig. 6.16

  35. Fig. 6.17

  36. Fig. 6.17

  37. General rules of globular proteins • All globular proteins have a defined inside and outside structure, hydrophobic AAs inside and hydrophilic AAs outside. • β-Sheets are usually twisted and wrapped into barrel structure. • The polypeptide chains can turn corner in a number of ways, to go from one β segment or a helix to the next. • Not all parts of globular proteins can be conveniently classified as helix, β sheet, or turn.

  38. Fig. 6.18

  39. Fig. 6.19

  40. Factors Determining Secondary and Tertiary Structure

  41. The Information for Protein Folding (Figure 6.20) • The information for determining the 3-dimensional structureofa protein is carried entirely in the amino acid sequence of that protein. • Native structure is the natural 3-dimensional structure of a protein. • Denaturation is a process for the lost of natural structure of a protein, along with many of its specific properties. • In a cell, a newly synthesized polypeptide chain will spontaneously fold into the proper conformation.

  42. Fig. 6.20