BIOL 541 1st Edition Lecture 2 Outline of Current Lecture Amino acids with side chains. 3 levels of protein structure.Current LectureAmino acids with OH and S side chains:Serine and threonine: Both contain OH side chain and neither can be ionized as pK value 13.However, in proteases can be ionized. O-linked sugar phosphorylation is seen as mitogenic signals: inother words, serine and threonine serve as metabolic signals.Cysteine: The S groups in this amino acid can kelate metal ions. This occurs in the electrontransport chain. The iron binds to covalent linkages. It can also perform as redox sensors.Proline: It is the only cyclic amino acid with a tight turn. It has perpendicular bonds that are destructive to the structure and are called as helix breakers or kinks in the helix. It is a sticky and stable structure with protein- protein interaction in the stable cis- conformation. It can flip between the cis and trans configuration and act as a molecular switch. It however needs an enzyme to switch from one form to another. It can be used in protein processing, for example, insulin cleavage results in alpha and beta chains. Also, proline enables proteases to give a clean cut.Selino cysteine: It has selenium instead of sulphur. It therefore needs redox enzymes. In the termination codon in structure of m.RNA if selino cysteine is present then it is not the stop codon and the chain elongation continues.3 levels of protein structure:Primary: Secondary: Tertiary:Amino acid sequence Uniform structure 3- D structurePeptide bonds Helix or B strand Hemoglobin (Hb)- 4 subunits Fold and overall 3- D Quaternary:4- subunits of Hb.Primary: There are peptide bonds. The electrons in the carbonyl are shared with the peptide bond. There is no rotation around the double bonds. Trans configuration has lessenergy due to steric hindrance. Further, proline can not be trans as energy level of ½ k.cal/ mol is preferred. Therefore, 6% cis confirmation is preferred.Secondary: Amino acids assume 3D structure in order to be stabilized. There are non- covalent bonds.a. charge- charge is a weak bond.b. Van der waals interaction between non- charged is seen.Dipole- dipole interaction between carbonyl is also observed.c. Hydrogen bonds are shared hydrogen between the lattice. The hydrogen of the amino group and oxygen of the carbonyl form the bond length of 0.3 Nm. This bond is intermediate for Van der Waals and ionic bond3 basic structures:1. Random structure: This is found in the test tube. 1/3 to ½ of the eukaryotic protein have 40 amino acids in the random structure. This increases the versatility and binds to ligands. This structure upon interaction increases the kinetics as more space gives rise to wider range of capture and speeds up association and dissociation. The rigid bonds require that all bonds be broken in order to break the protein. If the bonds are flexible, then they break one at a time. This enables protein modification. More protein is accessible in the random structure.Functions:a. Entrophic bristles maintain spacing in fibrinogen.b. Entrophic spring – An example is the largest protein in the muscle called as titin. The z- line of titin are stretched and contracted. Titin has regions of random structure for repeated foldings and refoldings that act as spring.c. Entrophic clocks are voltage gated channels that open upon depolarization. The globular tether plugs pore as shorter tether finds pore quickly and vice versa in order to control open time- acts as timer.Random structures are rich in proline and hydrophilic amino acids. No folding is seenas only hydrophobic folds.2. Beta structures: The extended chain interaction is seen through hydrogen bonding. In theanti- parallel Beta- structure has opposite direction where hydrogen is shared withoxygen of the carbonyl. Parallel structure is not properly lined and bends a little due to R- group interference with the bond. Polyglycine which is an artificial protein has even folds whereas natural proteins are sheet puckered.a. Beta pleated sheet- the R groups are thrown out as either above or below the plane and therefore do not interfere with the bonding. b. Beta helix- are also called parallel Beta sheet. It is a huge helix where the hydrogen bond is disrupted by compression. Hydrophobic amino acids stabilize it as well as D- amino acids stabilize it to avoid squishing the helix.c. Beta barrel has strands up and down.3. Alpha Helix structure: This forms the backbone and is stabilized by hydrogen bonds where nitrogen in one turn associates with oxygen in the adjacent turn.Characteristics of alpha helix:a. Pitch- Refers to the wavelength, it is the distance between 2 equivalent points on curve. It is the distance occupied by 1 amino acid. It is also due to presence of successive alpha carbon on nitrogen.b. Diameter- It refers to number of amino acids/ turn.c. Directions- Anti- clockwise or clockwise as well as right handed or left handed activity of the amino acid needs to be