Amino acids R-groups non-polar polar acidic basic proteins condensation between carboxylic acids and amines + + H2O carboxylic acid amine amide

Amides amides resonance structure dipeptide alanine glycine Ala-Gly +H2O

Polypeptides _ “backbone” _ H _ R _ H _ R _ H _ R H N1- C1- C1- N2- OH = O = O = O peptide bonds C-terminal residue N-terminal residue biological activity = structure protein structure 4 levels

Primary structure sequence of amino acids hemoglobin transports O2 and CO2 4 protein chains 300 amino acids Sickle cell anemia 6th amino acid from N-terminus R Glu Val -CH2CH2-CO2H -CH(CH3)2 water soluble water insoluble

Secondary structure hydrogen bonding backbone groups N1- C1- C1- N2- _ H = O OH R H-bond donors H-bond acceptors Two main secondary structures: -helix -sheet

Alpha helix = = Every C=O bonded to N-H 4 residues away forms a helix core is backbone R-groups outside 3.6 amino acids per turn C = O N H proline no H-bonding breaks helix = O C

Beta sheet Every C=O bonded to N-H far apart in 1o structure on different chains peptide chains extended side-by-side maximal H-bonding for anti-parallel chains small R-groups above and below the sheet if not -helix or -sheet random coil

Proteins Fibrous 1o structure amino acid sequence 2o structure - helix -sheet H-bonding between C=O and N-H of backbone - + some proteins only have 1o and 2o structure: fibroin (silk) -sheet insoluble in H2O keratin collagen hair skin - helix non-polar residues

Disulfide bonds cysteine -CH2-SH C H N C C H N C S-H H-S reduced [O] oxidized

Tertiary structure Primary structure sequence of amino acids Non-polar Ala-Phe-Ser-Ser-Val-Glu-His-Ile-Met-Arg-Asp-Val-His-Asn-Gly Ala- Phe- Ser- Ser- Val- Glu- His- Ile- Met- Arg- Asp- Val- His- Asn- Gly- Non-polar Polar Acidic or Basic Alanine Serine Glutamic acid Phenylalanine Histidine Arginine Valine Aspartic acid Isoleusine Asperagine Methionine Glycine

Tertiary structure arrange these in an -helix polar non-polar Ala-Phe-Ser-Ser-Val-Glu-His-Ile-Met-Arg-Asp-Val-His-Asn-Gly arrange these in an -helix Asp 11 Ser 4 His 7 Gly 15 polar Ser 3 non-polar Ile 8 interior Val 12 Asn 14 Arg 10 Glu 6 Phe 2 His 13 Ala 1 Val 5 Met 9 exterior

Tertiary structure interaction of the R-groups globular proteins + globular proteins proteins fold around non-polar groups hydrophobic residues inside polar and charged residues outside

Tertiary structure interactions of R-groups LDF 1. Hydrophobic interactions non-polar R-groups LDF 2. Hydrogen bonding polar R-groups between H-bond donors and acceptors 3. Ionic bonds (salt bridges) acidic and basic R-groups ion-ion 4. Covalent bonds (disulfide) cysteins

C-terminus N-terminus His Arg NH+ Asp -O-CH O = His Fe2+ Phe Ala CH3 Cys S Cys N-terminus Pro Pro

Denaturing treatments 1. Heat above 50-60oC frying egg sunburn 2. pH disrupt salt bridges approach pHI 3. detergents unfold globular proteins SDS - + Na+ SO4-

Denaturing treatments 4. reducing agents S-S SH HS oxidizing agents 5. Metal salts Hg+, Pb+, Ag+ S-Hg C = O _ O- Hg+ 6. H-bonding solvents alcohol acetone 7. “Chaotropes” urea guanidine