1. Proteins and Amino Acids 1

2. Biological Functions of Proteins Facilitate biochemical reactions Structural support Storage and Transport Immune protection Generate movement Transmission of nerve impulses Control growth and differentiation 2

3. Key Properties of Proteins Linear polymers of amino acids Contains a wide range of functional groups Forms complex assemblies of more than one polypeptide chain Versatile structure – some are rigid while others are flexible 3

4. Globular and Fibrous Proteins Globular protein Usually water soluble, compact, roughly spherical Hydrophobic interior, hydrophilic surface Globular proteins include enzymes,carrier and regulatory proteins Fibrous protein Provide mechanical support Often assembled into large cables or threads α-Keratins: major components of hair and nails Collagen: major component of tendons, skin, bones and teeth 4

5. General Structure of Proteins Twenty common a-amino acids have carboxyl and amino groups bonded to the α-carbon atom A hydrogen atom and a side chain (R) are also attached to the α-carbon atom 5

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7. Zwitterions Under normal cellular conditions amino acids are zwitterions (dipolar ions): Amino group = -NH 3+ Carboxyl group = -COO - 7

8. Stereochemistry of amino acids 19 of the 20 common amino acids have a chiral a-carbon atom (Gly does not) Threonine and isoleucine have 2 chiral carbons each (4 possible stereoisomers each) Mirror image pairs of amino acids are designated L (levo) and D (dextro) Proteins are assembled from L-amino acids (a few D-amino acids occur in nature) 8

9. Amino acid side chains Nine non-polar aa Six polar uncharged aa Five charged aa Three basic aa Two acidic aa Two aa with sulfur groups Four ring-forming aa Three have aromatic rings 9

10. Hydropathy Relative hydrophobicity of the amino acid The larger the hydropathy, the greater the tendency of an amino acid to prefer a hydrophobic environment Hydropathy affects protein folding: hydrophobic side chains tend to be in the interior hydrophilic residues tend to be on the surface 10

11. Acid-base chemistry of amino acids 11

12. Isoelectric point 12 pH at which the amino acid bears zero net charge

13. Titration curve of Histidine 13

14. Polymer of amino acid Peptide bond - linkage between amino acids is a secondary amide bond Formed by condensation of the α-carboxyl of one amino acid with the α-amino of another amino acid (loss of H 2 O molecule) 14

15. Resonance Structure of the peptide bond 15

16. Trans and Cis configuration of peptide bond Usually in the trans configuration 16

17. Dihedral Angle 17

18. Dihedral angle of proteins The phi angle is the angle around the -N-Cα- bond The psi angle is the angle around the -Cα-C- bond The omega angle is the angle around the -C 1 -N- bond (i.e. the peptide bond) 18

19. LEVELS OF PROTEIN STRUCTURE 19

20. Primary structure 20 >2CQG:A|PDBID|CHAIN|S EQUENCEGSSGSSGVKRAVQK TSDLIVLGLPWKTTEQDLKEY FSTFGEVLMVQVKKDLKTGHS KGFGFVRFTEYETQVKVMSQR HMIDGRWCDCKLPNSKQSQDS GPSSG

21. Secondary Structure 21

22. Alpha-helix 22

23. Right-handed and Left-handed α-Helix 23

24. Right-handed and Left-handed α-Helix 24

25. Beta-sheet 25

26. Determining 2 o structure: Ramanchandran Plot 26

27. Supersecondary structure: Motifs Secondary structures often group together to form a specific geometric arrangements known as motifs Since motifs contain more than one secondary structural element, these are referred to as super secondary structures 27

28. Domains stable, independently folding, compact structural units within a protein, formed by segments of the polypeptide chain, with relative independent structure and function distinguishable from other regions and stabilized through the same kind of linkages than the tertiary level Often each domain has a separate function to perform for the protein, such as: Bind a small ligand Spanning the plasma membrane (transmembrane proteins) Contain the catalytic site (enzymes) DNA-binding (in transcription factors) Providing a surface to bind specifically to another protein In some (but not all) cases, each domain in a protein is encoded by a separate exon in the gene encoding that protein. 28

29. Tertiary Structure Forces holding the tertiary (and higher order) structure together Salt bridge Covalent bond (disulfide bridges) Hydrophobic interaction Hydrogen bonding 29

30. Quaternary Structure 30

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32. Protein Folding 32

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