OBJ - Protein: Structural Organization

Question 1

Show the chemistry of peptide bond formation between two amino acid molecules

Answer 1

• covalent bond between COOH Carbob & the Amide N (Residue is attached to the alpha C)
• planar bond - Polypeptde main chain = Highly polar & each unit can H bond as both donor & acceptor

Question 2

Draw a planar peptide unit and show the rotational freedom allowed around the phi (φ) and psi (φ) angles

Answer 2

• Rigidity in peptide bonds
  
  • planar so no rotation because it’s a partial double bond

**need to balance flexibility & stabitity for proper folding

• Most phi/psi angles conformations are not allowed (Mostly in Trans configuration to avoid steric hindrance/interaction of R groups)
• Rotational Flexibility around alpha carbon
  
  • phi (φ) - the N side it’s attached too
  • psi (Y looking thing) - the COOH side it’s attached to
• Stabilized by Noncovalent (big 4) & Covalent (Dislfide bonds) Forces

Question 3

Define the structural hierarchy of proteins, and describe the covalent and noncovalent forces that stabilize primary, secondary, tertiary and quaternary structures

Answer 3

Structural Heirarchy:

1. Primary - peptide bonds between AA
   
   1. Primary structure dictates function b/c of AA sequence
2. Secondary - H bonds -> local conformations
3. Tertiary - disulfide bonds (hydrophobic residues tend to cluster away from aq environment -> interior of Globular proteins - H-phobic -> H bond with each other)
4. Quarternary Tertiary/Quart Structure - structure based drug design

Question 4

Describe the structural features of the two major periodic structures of proteins: α-helix and β-sheet. Differentiate between them with special emphasis on the nature of hydrogen bonding

Answer 4

α-helix:

hydrogen bonds are intra-helical - stay “isolated” to their corkscrew right handed helix i.e. Myoglobin

1 residue = 100 degrees of rotation each turn = 3.6 residues->

n+4 bonding pattern (vertical H bonding stabilizes helix coil -side chains stick out & don’t interfere with helix

β-sheet

hydrogen bonds are prone to inter strand AND inter-sheet bonding can be parllalel/antiparallel/mixture

multiple beta strands make a beta sheet; pleated in nature

Question 5

Differentiate between parallel and antiparallel β-sheets

Answer 5

Parallel - the Amine terminals are on the same side & the Carboxylic terminals are on the same side

Antiparallel: One Amine terminal is is next to a carboxylic terminal in the sheet PIC

Question 6

Explain the significance of loop regions and turns in protein structure and function

Answer 6

• Loops: definitive shape due to AA order, but no repeating structures; connect α-helix and β-sheet
• rich in polar & charged residues Hairpin loops/reverse turns = connecting adjacent antiparallel beta sheets
• often found at enzyme active sites/surface of the molecule
• ex: anitbodies -> adds flexibility

Nonrepetivie = Loop/random coil

Repetitive structures -> helix & sheets

Question 7

Describe why proline is not a good helix former

Answer 7

• the cyclic N in proline can’t H bond creates steric hindrance
• tends to end up as the first turn of the alpha helix, otherwise it gets a significant kinked
• no preference for trans/cis b/c steric hindrance is always there

Question 8

Describe the molecular basis of prion protein aggregation

Answer 8

Prp-Sc: disease causing form of the protein has same AA composition byt folds differenly instead of alpha helices -> B sheet structure which is very resistant to degradation & aggregates because of the difference in H bonding of the secondary strutures

Question 9

Identify the main chain carbon atoms, the amino acid side chains, the N-terminal and the C-terminal ends of a given polypeptide

Answer 9

C’s: COOH & alpha C (bound to residue) N terminal - side that ends with unbound amide C terminal - side that ends with unbound COOH

Question 10

**3 Major types of Proteins

Answer 10

Globular (i.e Hb) Fibrous (i.e. Collagen Membrane Proteins (i.e. cytochrome bc1 complex)