1. Review of Basic Principles of Chemistry, Amino Acids and Proteins Brian Kuhlman: bkuhlman@email.unc.edu The material presented here is available on the course web page.

2. Some basic principles of chemistry distances are typically measured in angstroms (Å). (1 Å = 1x10 -10 meters). 1.38 Å One hydrogen weighs 1 dalton (Da). The average amino acid weighs 110 daltons. A one hundred residue protein weighs ~11,000 Da, or 11 kilodaltons (kD). A one hundred residue protein is generally between 30 and 50 Å wide.

3. a covalent bond: a bond in which electrons are shared between two atoms (these are strong bonds and an enzyme is often required to make or break them at physiological conditions).

4. electronegativity: the electronegativity of an atom is its ability to attract electrons. O > N > C = S > H O  H  A polar molecule has an uneven distribution of charge. This occurs because some atoms in the molecule are more electronegative than others. O  H  The partial charges on polar molecules generally interact favorably with each other.

5. hydrogen bond: a special bond formed between a hydrogen atom in a polar bond such as O-H or N-H and electronegative atoms like O and N (~ 2 kcal / mol ). Water can form hydrogen bonds. In this example O is the hydrogen bond acceptor and N is the hydrogen bond donor. pH: pH = -log[H + ]. A pH of 7 is neutral, low pH is acidic and high pH is basic. At low pH there is a high concentration of protons (H + ) in solution and a low concentration of OH -. The reverse is true at high pH.

6. acid-base reactions. An acid donates protons and a base accepts protons. An acid is often in equilibrium with its conjugate base. The concentration of the two species (acid and conjugate base) depends on the pH and the pKa of the molecule. HA  H + + A - pH 7 OH pH 2 acid conjugate base pKa: the pH at which half the molecules are protonated and half are de-protonated. Aspartic Acid pKa = 3.9

7. B.Amino acids Proteins are polymers constructed from the 20 “standard” amino acids. All amino acids share a set of atoms that make up the backbone of the protein chain.

8. Hydrophobic or Non-Polar Amino Acids Glycine (Gly, G) Alanine (Ala, A) Valine (Val, V) Isoleucine (Ile, I) Leucine (Leu, L) Phenylalanine (Phe, F) Tyrosine (Tyr, Y) Trptophan (Trp, W) Methionine (Met, M) Proline (Pro, P) C O Backbone bonds: red Side chain bonds: black

9. Polar or Hydrophilic Amino Acids Histidine (His, H) Aspartic Acid (Asp, D) Glutamic Acid (Glu, E) Lysine (Lys, K) Arginine (Arg, R) pKa = 6.0 pKa = 3.9 pKa = 4.1 pKa = 10.8 pKa = 12.5 Serine (Ser, S) Threonine (Thr, T) Cysteine (Cys, C) Asparigine (Asn, N) Glutamine (Gln, Q)

10. Amino Acids with Special Properties Gly: more flexible than the other amino acids Pro: more rigid than the other amino acids Cys: two cysteines can form a bond between their sulfur atoms (a disulfide bond) Asp, Glu: negative charge at pH 7 Lys, Arg: positive charge at pH 7 His: pKa near 6.0 (positive charge below pH 6, neutral above pH6)

11. The pKa of a group can be perturbed by the rest of the protein + Will have a pKa lower than its natural pKa of 3.9. - Will have a pKa higher than its natural pKa of 3.9.

12. C. Proteins are molecules that consist of one or more polypeptide chains. Proteins with very few amino acids are typically referred to as peptides. peptide bond N-terminusC-terminus

13. What do proteins look like? beginning of the protein, N- terminus end of the protein, C-terminus  -strand, all 4 strands together make a  -sheet  -helix Amino acid sequence of protein G: MTYKLILNGKTLKGETTTEAVDAATAEKVFKQYANDNGVDGEWTYDDK TFTVTE Example: small bacterial protein called protein G

14. What do proteins look like? beginning of the protein, N- terminus end of the protein, C-terminus  -strand, all 4 strands together make a  -sheet  -helix Amino acid sequence of protein G: MTYKLILNGKTLKGETTTEAVDAATAEKVFKQYANDNGVDGEWTYDDK TFTVTE Example: small bacterial protein called protein G

15. Classifying protein structure 1. Their primary structure is the amino acid sequence of the polypeptide chain. 2. Secondary structure is the local spatial arrangement of a polypeptide’s backbone atoms. Common secondary structures are  -helices and  -strands. 3. Tertiary structure refers to the three-dimensional structure of the entire polypeptide chain. 4. Some proteins are composed of two or more polypeptide chains. The spatial arrangement of these chains is a protein’s quaternary structure.

16. Protein Secondary Structure: The  -helix Purple: Hydrogen Bonds Red: Oxygen Dark Blue: Nitrogen Light Blue: Hydrogen Green: Carbon

17. Protein Secondary Structure: The  -helix Purple: Hydrogen Bonds Red: Oxygen Dark Blue: Nitrogen Light Blue: Hydrogen Green: Carbon i i+1 i+2 i+3 i+4 A standard  -helix has hydrogen bonds between residues i and i + 4.

18. Protein Secondary Structure: The  -strand Purple: Hydrogen Bonds Red: Oxygen Dark Blue: Nitrogen Light Blue: Hydrogen Green: Carbon  -sheet  -strands come together to form  -sheets (the interaction can be either parallel or anti-parallel).