Lecture 3+4: Conformation and weak interactions

Question 1

What is a Macromolecule?

Answer 1

polymers with molecular weight above 5000 assembled from simple precursors
i.e. proteins, nucleic acids, large polysaccharide i.e. cellulose, starch

Question 2

What happens in sickle cell anaemia?

Answer 2

Glutamic acid is mutated to valine
negatively charged to highly non polar amino acid
Primary structure mutation determines secondary structure and so on
hydrophobic amino acid on surface of Beta-subunit = a sticky patch
exposed hydrophobic molecules = stick together in water - hydrophobic effect
in normal haemoglobin formation of normal tetramer whereas in SCA 4 subunits the bet subunits have exposed patches due to valine which is hydrophobic
in normal haemoglobin in RBC go their own was as have polar residues on surface whereas SC sticky patches allows them to form chains and crystals = polymerise = precipitate out of cytoplasm = build up in spleen = enlargement then fibrosis of spleen among other things - plurotrophic affect
rapid destruction of sickled cells = anaemia +
clumping of cells

Question 3

autosomal disease

Answer 3

not on the sex gene so passed onto daughter or son at same chance

Question 4

amino acid side chains

Answer 4

1. non polar - don’t interact with water
   so buried inside protein
2. polar - hydrogen bond acceptors/donors
3. aromatics - absorb light in UV range
   allow us to measure amount of proteins in a sol. using a spectrophotometer
4. -ve r groups - acidic and polar side chains
   pK1 - Alpha carboxy group
   pK2 - amino group
   pKr - side chain carboxy group
5. +vely charged - His pk lower than neutral

Question 5

difference between configuration and conformation

Answer 5

configuration (D+L) - covalent structure
determined by double bonds or chiral centres, planar groups +
cannot be changed without breaking and forming bonds

conformation - spatial arrangement of groups that are free to assume different positions in space without breaking bonds = bond rotation freedom

rotation about covalent bond s(torsion angles)

Question 6

peptide bond nature and formation

Answer 6

1. the longer the C=N double bond the shorter the c-N singe bond
2. O = C-N-H form a plane as their electrons are delocalised = resonance
3. trans configuration alpha carbons on 2 opposite sides = is more favourable due to reduced steric hinderance

condensation of carboxylic acids of one amino acid with the amine of the next amino acid = endergonic reaction as requires free energy input
therefore reverse is exergonic

Question 7

stereochemistry

newman projections link to protein folding

Answer 7

perspective view as you would observe along the C-C axis
there are diff conformations that the substituent groups could be at (180 degrees) = most stable whereas least stable is when they overlap due to repulsion = potential energy is highest

going from disorder to a well determined set of torsion angles

Question 8

what determines native conformation

Answer 8

native - preferred conformation

determined by weak interactions:

1. enthalpic - hydrogen bonds, ionic interactions (salt bridges), van der Waal forces - temporary +ve/-ve charge = dipole
2. entropic - the hydrophobic effect - water forms a clathrate (cage of water) around amphipathic molecules hydrophobic molecules = energetically unstable. more favourable if he molecules cluster = minimise surface area of lipids available for interaction with water = less water molecules have lost degrees of freedom

delta G (<0)= Delta H (as negative as possible) - T*delta S(as positive as possible)

Question 9

how can the entropic cost be lowered if it cannot cluster with other molecules

Answer 9

polypeptide changes in conformation by rotating torsion angles to bring the hydrophobic amino acids close together an minimize the clathrate- bury within core of protein