Friday 9 30 05

9/30/2005 Lecture
• {Review from Wed: alpha helix structure has stabilizing bond between nitrogen and carboxyl. The alpha-carbon holds them in a plane. Figure 4-2. Each H bond form has stability to the structure. }
• Figure 4-7 Beta structure formed when 2 chains are superimposed and each hydrogen is in a bond. Beta structure gives a long range of interactions. Give large two dimensional chains.
• Alpha-carbon is not in the plain, gives a pleat, ripple look.
• R-group not involved. Alternate from the plane, in and out of the plane. R-group charges do interact with each other, so they are adjacent to each other in the beta-sheet.
• Antiparallel has a chain running in an opposite form, because of opposite polarity. The hydrogen bonds are also aligned. Most common beta-conformation. More stabilizing energy because of the H bond alignment.
• Parallel has all strands running in the same direction. Has an enteric difference because the strength of the H bond is lowered. The H bonds are no collinear which makes them not stable.
• Gamma turns are very rare; it is a U-turn (180 degrees) with only three residues.
• Beta turns are U-turns with 4 residues, which have less strain. There is only 1 hydrogen bond between alpha-carbon 1 and alpha-carbon 4.
• Figure 4-8a There are two types of turns. Type I is on surface of proteins, where the hydrogen from alpha-carbon 2 and alpha-carbon 3 form with water, forms water soluble proteins. Type II is less frequent. The alpha-carbon 3 is always glycine so that steric crowding is minimized.
• Figure 4-8b Proline isomers- are the “weirdo” amino acid. There is a cis and trans form, the cis form, which happens 5-10%, the chain breaks or the helix of beta-structure makes a wrong turn.
• Figure 4-9 Stric interference the plot validated by the structures found.
• Figure 4-10 There are no rules for protein in structure there are only tendencies of how they will fold. Proteins are context dependent.
• Figure 4-11 Fibrous proteins, keratin alpha helix in a right hand helix. Form two chain coiled given strength; both strains running in the same direction inter-weaving in a left hand helix form. The two strains are compressed to make it more stable. Then protofilaments can combine to make protofibril, which is a higher level structure of mammal hair.
• Box 4-2 Disulfide bonds keep hair stable so to perm hair, you use chemicals to break those bonds which allow you to shape hair.
• Figure 4-15 Beta conformation is longer than alpha helix. The globular form is smallest. Spiders use Ala and Gly to form a beta structure that can bond closer together.
• Figure 4-16 Myoglobin in sperm whales. To see this structure, you need to go to the class web site and download Ras or Chime so that you can look up and view 3D pictures of proteins. Instructions are on the website. We will use these programs for some homework problems.
• Figure 4-17 The structure of heme. Do not need to know the structure, but it is a great example of evolution. The electron carrying citron in the middle moved just enough for Oxygen to fit but not for carbonmonxide to stick.

Wednesday 9 28 05

{Section notes 9/28/05
Office hours and email are posted on website.
Show as much work possible on homework for credit.
Homework tips:
Problem 1: Histidine has a lone pair of electrons on the N that is not boded to H in the book. This lone pair can pick of a H and take on a charge. This will help with parts B and C.
Problem 2: You need to use both pKa’s and the pI (which you need to find). Then use the Henderson-Hasselbalch equation (page 67.) }

9/28/05
• Different types of protein – catalytic protein in plants, transport proteins in hemoglobin, and structural proteins in skin. Figure 3-1
• For two amino acids to bond together, H2O is removed. It has an amino- terminal end and a carboxyl terminal end (you read the protein from amino to carboxyl.) The bond form is extremely stable and it retains in polarity, meaning the NH3 stays positive and the COO stays negative on the ends. The R group is not involved in the bonding.
• Polypeptide is linear structure of protein. A three letter code is used for proteins as a short hand for writing them. Table 3-3 Random distributions in proteins, not equal amounts.
• Number of bonds = amino acids -1
• Table 3-2 Molecular Data on Some Proteins. Shows their weight, how many residues and the number of polypeptide chains.
• Table 3-4 Conjugated proteins. Proteins and prosthetic groups come together to make different functioning proteins.
• Fred Sanger in the 1950’s used insulin to map the amino acids. He knew the molecular weight and started at the amino end and pulled one amino acid off at a time to chemically purify the two chains of insulin so that he could sequence.
• Primary structure- amino acid residues
• Secondary structure- alpha-helix
• Tertiary structure – polypeptide chains
• Quaternary structure – assembled subunits (All shown in Figure 3-16)
• In the 1940’s, X-ray diffraction studies shows that the proteins were 3-D.
• Water soluble proteins could also be crystallized and still be functional, showing that they proteins where is some 3-D form.
• Protein folding is very important, determines function. Will fold by non-covalent bonds in high-order folding. Primary folding is from covalent bonds.
• When folding, it is important that water is excluded because it can denature the protein. Water excludes itself because it forms stronger H bonds with other water molecules, so it finds other water to bond with, making sure it does not get in the way of the other bonds.
• Folding of Proteins
• The carbonyl oxygen has a partial negative charge and the amide nitrogen has a partial positive charge, setting up a small electric dipole. Virtually all peptide bonds in proteins occur in this Tran configuration,
• Figure 4-2 Because of this dipole and double bonds in the peptide, there are two rotation angles on the alpha carbon, creating 2 different plate alignments. (This eliminates any rings forming because of angle strain.)
• Figure 4-3 This ramachandran plot shows the different combinations of the angles that are favored thermodynamically.
• Figure 4-4 folding in an alpha helix was just a guess at first and had to be proven, it was right.
• Because of the acceptor and donor still present in the backbone of the helix, higher structures were possible because of more H bonding.
• Box 4-1 Right handed helix, thumb is pointing to the amino terminal end and fingers turn counter clock wise up the amino acids. Right handed helixes are more favored than left.
• R groups are all facing out. The sequence depends on stability of the R group. R groups can attract or repel each other. Just another factor in folding.
• Alpha helixes have dipole movement toward amino terminus, which effects which way the R group is pointing depending on it charge.
• Antiparallel- beta structure in a sheet form. Figure 4-7 (He stopped talking because time was out. He will continue here on Friday 9/30.)

Monday 9 26 05

9/26/05
• There are four different types of bonds:
1. covalent bonds- strong interactions
2. electrostatic bonds- cations and anions in aqueous solution.
3. hydrogen bond – form between hydrogen donors and hydrogen acceptors
4. van der Waals bonds – weak, non-polar interactions, not good in aqueous solution.
• Water must be excluded in major catabolic pathways so it does not compete for bonds. Very important for the formation of complex proteins.
Amino Acids and Proteins
• In all cases but one all proteins are optical active. Glycine is the exception because it has hydrogen for its R group.
• Alanine is the simplest, optical active, protein because it has CH3 for its R group.
• Figure 3-3 L form is standard, this means the carboxyl group is north and the amine group is east. The L form is what is commonly found in nature. D form is rare, and when found it is usually changed to the L form with enzymes.
• Figure 3-5 The 20 amino acids are subdivided into 4 groups based on the R chain. (He wants you to know all 20 and what makes them chemically different, he said names are not so important.)
• Non-polar, aliphatic (hydrophobic) R group – glycine, alanine, praline, valine, leucine, isooleucine, methionine.
• Aromatic R group – Phenylalanine, tyrosine, tryptophan. All can absorb UV light. Tryptophan absorbs more than tyrosine and phenylalanine absorbs the least amount. Figure 3-6 shows the absorption levels of tryptophan and tyrosine.
• Polar, uncharged R groups – serine, threonine, cystine, asparagines, and glutamine.
• Positively charge R groups- lysine, arginine, histidine. These are basic R groups.
• Negatively charged R group – aspartate, glutamate. Acidic R groups, second carboxyl group attached.
• Cysteine has a self hydrogenating group with SH
• Figure 3-7 2 cystEINE can form a disulfide bond to make cystINE. Similar words, very different compounds, be careful.
• Figure 3-8 The uncommon amino acids: 4-hydroxyproline, 5-hydroxyproline, 6-N-methyllysine, y-carboxyglutamte, desmosine, selenocysteine.
• Figure 3-9 Nonionic and zwitterionic forms. Zwitterionic is common in neutral pH. They differ because the H is pulled off the OH, given O a negative charge that balances with the positive N.
• Isoelectric point – where the pH at which there is no electrical charge on the molecule. To find it, you take the to pKa from the titration and average them. What happens when there are three? (He did not answer his own question, he left it up to us.)
• Figure 3-10 The titration graph shows the two pKa’s where there is a buffering going on and the pI (isoelectric point) is in the middle of the sharp incline.
• Figure 3-11 This chart shows the power of proteins. If you look at the acetic acid, it has a pH of 4.8. But the alpha-Amino acid, with the acetic acid on it, has a higher pH 2.34 because the N from the amine is pushing the H off. Looking at the Methylamine, it is very basic with a pH of 10.6. The alpha-Amino acid has a lower pH at 9.6 because of the carboxyl group pulling the H towards it.
• Histidine is the only protein that acts as a buffer in biological neutrality, making it very important to catabolic pathways. Its pKa is close to 6.

Friday 9 23 05

(All the figures used in lecture are listed in the notes. They can be found in the book. )
9/23/05
• Class website: bio.classes.ucsc.edu/bio100/
• At this website is contact information for the professor and the TA’s.
• Every week there is a problem set on E-RES. The password is slugsrule
• This lecture was an introduction to the “fascinating” world of biochemistry.
• Deductive science/reason is like the game of clue; you have all you facts in line before you state you conclusion.
• Inductive science/reason is like the Wheel of Fortune; you have holes and you try to guess before everything is in it’s place
• You need both types of reason in science, they work hand in hand.