3. Proteins 3D Structure COPY Flashcards
Define
- protein conformation
arrangement in space of its constituent atoms which determine the overall shape of the molecule
Define
- native protein
Proteins in their natural state with intact structure that is not altered by heat, chemicals, enzyme reaction, or other denaturants are named “native proteins”.
Define:
- protein stability
the energy difference between the folded and unfolded state of the protein in solution. Remarkably, the free energy difference between these states is usually between 20 and 80 kJ/mol, which is of the magnitude of one to four hydrogen bonds.
Thus the stability of a protein is determined by large number of small positive and negative interaction energies.
Define:
- hydrophobic interaction
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules
Define:
- hydrogen bond
a weak bond between two molecules resulting from an electrostatic attraction between a proton in one molecule and an electronegative atom in the other.
Define
- ionic interaction
- van der Waals interaction
- Ionic interaction
- type of linkage formed from the electrostatic attraction between oppositely charged ions in a chemical compound.
- Van der Waals interaction:
- Van der Waals forces are weak intermolecular forces that are dependent on the distance between atoms or molecules. These forces arise from the interactions between uncharged atoms/molecules.
- Weak attractions of two dipoles that bring the nuclei closer -Electron clouds will repel each other as nuclei are brought closer together
- At point where net attraction is maximal, nuclei are in van der Waals contact
- Each atom has a characteristic van der Waals radius (a measure of how close that atom will allow another to approach
NEEDS ANSWERED
- Describe how maximizing numerous weak interactions provides the dominant stabilizing force in protein structure.
- Crucial to macromolecular structure and function -
- Individually weak, but with a strong cumulative effect -
- For macromolecules, the most stable structure is usually that in which weak interactions are maximized -
- Folding of a polypeptide or polynucleotide chains into a 3D shape is determined by this principle -
- The binding of an antigen to a specific antibody depends on the cumulative effects of many weak interactions
NEEDS ANSWERED
- State two general rules about weak interactions underlying the structural patterns observed in soluble proteins.
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- Explain the chemical basis for the planarity of the peptide bond and the six atoms forming the peptide group.
- Peptide group has a rigid planar structure as a consequence of resonance interactions that give the peptide bond 40% double bond character
- Define the torsion angles φ and ψ in the polypeptide chain. Define the conventions for defining the angles of 0° and 180°
- Torsion angles (dihedral angles) or rotation angles:
- Calpha – N bond = φ (phi) F
- Calpha – C bond = ψ (psi) Y
By convention: both phi and psi are 180° when polypeptide chain is in fully extended conformation and increase clockwise viewed from Calpha
F and y defined as 0° when the two peptide bonds flanking that carbon are in the same plane (w/ atoms 1 and 4 in cis arrangement)
- Describe the physical limits on values of φ and ψ, and how those limits are illustrated in a Ramachandran plot.
- Sterically constrained
- Certain rotations around the psi or phi angles will cause amide hyrogen, carbonyl oxygen or substitu of Calpha to collide
- ie bring atoms closer than the van der waals distance
- Ramachandron plot:
- summarizes the sterically allowed values of phi and psi
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- summarizes the sterically allowed values of phi and psi
- Explain why proline and glycine have different Ramachandran plots from alanine.
Gly: the only residue without Cbeta atom = much less sterically hindered = permissible range of psi and phi covers larger area of ramachandran diagram
Pro: Cyclic side chain limits range of phi to around -60° = most conformationally restricted amino acid residue
- List the physical parameters of the α-helix, including characteristic φ and ψ angles, handedness and residues per turn.
- Right-handed
- ideally: φ (phi) = -57°
- ψ (psi) = -47°
- 3.6 residues per turn
- R-groups point outward and downward from the helix
- Van der waals interactions and H-bonding stabilize
Describe the main-chain hydrogen bonding pattern that stabilizes the α-helix.
Backbone hydrogen bonds are arranged such that the peptide C=O bond of the nth residue points along the helix axis toward the peptide N-H group of the (n+4)th residue
= STRONG H-BOND
- Describe the helix dipole and how it is generated by atoms in the polypeptide backbone.
A helix has an overall dipole moment due to the aggregate effect of the individual microdipoles from the carbonyl groups of the peptide bond pointing along the helix axis.
- Transmitted through intrachain H-bonds
- Outline different ways that the nature of amino acid R-groups can affect the stability of an α-helix.
The R groups of the amino acids stick outward from the α helix, where they are free to interact
- Ala, Glu and Met have highest propensity for alpha helix formation
- Asp and Glu often at N-terminus
- Lys and Arg often at C-terminus (charge complementarity)
- Pro and Gly have lowest
- Pro residues:
- introduce a kink
- proline is sometimes called a “helix breaker” because its unusual R group (which bonds to the amino group to form a ring) creates a bend in the chain and is not compatible with helix formation
Steric clashes between sequential large branched residues (Ile and Tyr) destabilize alpha helices
- Often flanked by Asn and Gln = sidechains fold back to form h-bonds == helix capping
Compare the structures of α-helices and β-sheets in terms of main-chain shape, hydrogen bonding pattern and location of R-groups.
B-sheet:
- H-bonding occurs between neighbouring polypeptide chains rather than within one (as in alpha helix)
- rippled or pleated (sheets formed by H-bonds between strands)
- Right handed
- R-groups extend perpendicularly to the plane of the sheet w/ successive chains on opposite sides
Alpha Helix
- Right-handed
- ideally: φ (phi) = -57°
- ψ (psi) = -47°
- 3.6 residues per turn
- R-groups point outward and downward from the helix
- H-bonding
- List the differences between parallel and antiparallel β-sheets.
- Antiparallel Beta Sheet:
- Neighboring hydrogen bonded polypeptide chains run in opposite directions
- (f,y) near (-140, +140)
- Parallel Beta sheet
- H-bonded polypeptide chains run in opposite direction
- (f,y) near (-120, +120)
- Describe the shape and hydrogen bonding pattern of a β turn.
commonly observed features of beta turns are
- a hydrogen bond between the C=O of residue i and the N-H of residue i+3 (i.e, between the first and the fourth residue of the turn)
- Backbone H-Bond
- strong tendency to involve glycine and/or proline
- Always (almost) occur at protein surface
- Type I or Type II (differ by 180° flip of peptide unit)
- State why Gly and Pro residues are frequently found in β-turns.
- Pro is often Residue 2 of both Type I and type II beta turns because it can assume the required conformation
- Proline is typically found in bends, unstructured regions between secondary structures.
- Gly:
- Type II turns: oxygen atom of residue two crowds the Cbeta atom = glycine (small)
- can adopt the necessary (80°, 0°) at i+2
- Statistical analysis revealed that Pro and Gly residues are favored in β-turns presumably due to the cyclic structure of Pro and the flexibility of Gly
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