1. Chapter 3. Protein structure and function

2. Proteins are the most versatile macromolecules in living systems. serve crucial functions in essentially all biological processes. functions as catalysts.

3. Several key properties of proteins 1.Proteins are linear polymers built of monomer units called amino acids. 2.Proteins contained a wide range of functional groups. (alcohols, thiols, thioesters, carboxylic acids, basic groups) 3. Proteins can interact with one another and with other biological macormolecues to form complex assembles. 4. Some proteins are quite rigid, whereas others display limited flexibility.

5. - Only L amino acids are found in proteins. Proteins are built from a repertoire of 20 amino acids The L and D isomers of amino acids.

6. Ionization state as a function of pH

8. Peptide bonds are quite stable kinetically because the rate of hydrolysis is extremely slow Primary structure: amino acids are linked by Peptide bonds to from polypeptides chains

9. Amino acid sequences have direction

10. Main chain or backbone: H bond donor-NH, H bond acceptor-CO, Side chain: dependent on residues The mean molecular weight of amino acid residue is ~110 g/mol (Da) Components of polypeptide chain

11. Disulfide bond: Cross-links

12. Amino acid sequence of bovine insulin Intra-molecule disulfide bond Inter-molecule disulfide bond

13. Proteins have unique amino acid sequences knowing a.a. sequences is important for several reasons. Knowledge of AA sequence 1. is essential to elucidating its mechanism of action. 2. determine the 3D structures of proteins 3. is a component of molecular pathology 4. reveal much about its evolutionary history

14. Peptide bond is planar Polypeptide chains are flexible yet conformationally restricted.

15. Peptide bond has considerable double-bond character, which prevents rotation about this bond

16. Almost all peptide bonds in proteins are trans Steric clashes between groups attached to the alpha-carbon hinder formation of the cis form

17. Trans and cis X-pro bonds. The energies of these froms are realtively balaced because stric clashes occur in both forms Most common cis peptides are X-proline linakges

18. In contrast with peptide bonds, the bonds btwn the amino group and the a-carbon atom and btwn the a-carbon and C-group are single bond. This freedom of rotation about two bonds of each amino acid allows proteins to fold in many different ways.

19. By convention, both φand ψare defined as 0 when the two peptide bonds flanking that carbon are in the same plane and positioned as shown.

20. The conformations of peptides are defined by the values of φand ψ. Conformations deemed possible are those that involve little or no steric interference, based on calculations using known van der Waals radii and bond angles.

21. Secondary Structure: Spatial arrangement of amino acid residues Polypeptide chains can fold into regular structures such as the alpha helix beta sheet, and turns and loops.

22. Alpha Helix Structure of  -helix

23. The CO group of each amino acid forms a hydrogen bond with the NH group of the amino acid that is situated four residues ahead in the sequence. Q) Why does the α helix form more readily than many other possible conformations? A) in part, an α helix makes optimal use of internal hydrogen bonds. H-bond scheme for an  -helix

24. Right handed Helices: 손가락 기준으로 시계반대방향 Left handed Helices: 손가락 기준으로 시계방향

25. Five different kinds of constraints affect the stability of an α helix (1)the electrostatic repulsion (or attraction) between successive amino acid residues with charged R groups (2) the bulkiness of adjacent R groups (3) the interactions between R groups spaced three (or four) residues apart (4) the occurrence of Pro and Gly residues (5) the interaction between amino acid residues at the ends of the helical segment and the electric dipole inherent to the α helix.

26. β-sheets A β-strand is almost fully extended rather than being tightly coiled as in the α helix. Structure of a β-strand

27. Anti-parallel arrangement Parallel arrangement Simple H-bonds Complicated H-bonds

28. Polypeptide chains can change direction by making reverse turns or loops Reverse turn =  -turn = hairpin bend Loops = omega Loops

29. Beta-Turn: connect the ends of two adjacent segments of an antiparallel β sheet Structure of a reverse turn H-bond: CO of i and NH of i+3

30. Loops: no structural characteristics, more elaborate structurea responsible for chain reversal Loops on a protein surface Surface loops that mediate interactions with other molecules Antibody

31. Tertiary structure: Protein Architecture The overall three-dimensional arrangement of all atoms in a protein Fibrous proteins, having polypeptide chains arranged in long strands or sheets ex: alpha-keratin Globular proteins, having polypeptide chains folded into a spherical or globular shape ex: myoglobin

32. Myoglobin: the first protein to be seen in atomic level Three dimensional structure of myoglobin

33. Quaternary structure: Spatial arrangement of subunits and the nature of their interactions The  teramer structure of human hemoglobin

34. The amino acid sequence of a protein determines its three dimensional structure 1.Amino acids have different properties for forming  -helix,  sheets and  turns 2. Protein folding is highly cooperative process. 3. Proteins fold by progressive stabilization of intermediates rather than random search 4. Prediction of three D structure from sequence remains a great challenge. 5. Protein modification and cleavage confer new capabilities