chapter 4 Flashcards
Favorable Interactions in Proteins
Hydrophobic effect
Release of water molecules from the structured solvation layer around the molecule as protein folds increases the net entropy
Hydrogen bonds
Interaction of N-H and C=O of the peptide bond leads to local regular structures such as α-helices and β-sheets
London dispersion
Medium-range weak attraction between all atoms contributes significantly to the stability in the interior of the protein
Electrostatic interactions
Long-range strong interactions between permanently charged groups
Salt-bridges, esp. buried in the hydrophobic environment strongly stabilize the protein
Structure of the Peptide Bond
Structure of the protein is partially dictated by the properties of the peptide bond
The peptide bond is a resonance hybrid of two canonical structures
The resonance causes the peptide bonds
-to be less reactive compared to esters, for example
-to be quite rigid and nearly planar
-to exhibit a large dipole moment in the favored trans configuration
Resonance in the Peptide Bond
Each peptide bond has some double-bond character due to resonance and cannot rotate. Although the N atom in a peptide bond is often represented with a partial positive charge, careful consideration of bond orbitals and quantum mechanics indicates that the N has a net charge that is neutral or slightly negative.
The Rigid Peptide Plane and the Partially Free Rotations
-Rotation around the peptide bond is not permitted
-Rotation around bonds connected to the alpha carbon is permitted
-φ (phi): angle around the α-carbon—amide nitrogen bond
-ψ (psi): angle around the α-carbon—carbonyl carbon bond
-In a fully extended polypeptide, both ψ and φ are 180°
FIGURE 4-2b The planar peptide group. (b) Three bonds separate sequential α carbons in a polypeptide chain. The N—Cα and Cα—C bonds can rotate, described by dihedral angles designated Φ and Ψ, respectively. The peptide C—N bond is not free to rotate. Other single bonds in the backbone may also be rotationally hindered, depending on the size and charge of the R groups.
Distribution of φ and ψ Dihedral Angles
-Some φ and ψ combinations are very unfavorable because of
-Some φ and ψ combinations are more favorable because of
-A Ramachandran plot shows the distribution of φ and ψ dihedral angles that are found in a
Some φ and ψ combinations are very unfavorable because of steric crowding of backbone atoms with other atoms in the backbone or side chains
Some φ and ψ combinations are more favorable because of chance to form favorable H-bonding interactions along the backbone
A Ramachandran plot shows the distribution of φ and ψ dihedral angles that are found in a protein
–shows the common secondary structure elements
–reveals regions with unusual backbone structure
Secondary Structures
-Secondary structure refers to a local spatial arrangement of the polypeptide backbone
-Two regular arrangements are common:
–The α helix
stabilized by hydrogen bonds between nearby residues
—The β sheet
stabilized by hydrogen bonds between adjacent segments that may not be nearby
-Irregular arrangement of the polypeptide chain is called the random coil
The α Helix
-Helical backbone is held together by
-_____-handed helix with
-Peptide bonds are aligned roughly
-Side chains
-Helical backbone is held together by hydrogen bonds between the backbone amides of an n and n+4 amino acids
-Right-handed helix with 3.6 residues (5.4 Å) per turn
-Peptide bonds are aligned roughly parallel with the helical axis
-Side chains point out and are roughly perpendicular with the helical axis
The α Helix: Top View
-The inner diameter of the helix (no side chains) is about
-The outer diameter of the helix (with side chains) is
–Residues 1 and ___ align nicely on top of each other
-The inner diameter of the helix (no side chains) is about 4–5 Å
–Too small for anything to fit “inside”
-The outer diameter of the helix (with side chains) is 10–12 Å
–Happens to fit well into the major groove of dsDNA
-Residues 1 and 8 align nicely on top of each other
–What kind of sequence gives an α helix with one hydrophobic face?
Sequence affects
-Not all polypeptide sequences adopt
–Small hydrophobic residues such as __ and __ are strong helix formers
-Helix breakers?
-Attractive or repulsive interactions between side chains 3–4 amino acids apart will affect
helix stability
-Not all polypeptide sequences adopt α-helical structures
-Small hydrophobic residues such as Ala and Leu are strong helix formers
-Pro acts as a helix breaker because the rotation around the N-Ca bond is impossible, no N-H for H-bonding
-Gly acts as a helix breaker because the tiny R-group supports other conformations
-Attractive or repulsive interactions between side chains 3–4 amino acids apart will affect formation
-An α helix is not formed due to strong repulsion of adjacent
-Lys and Arg are positive at
Bulk and shape of ___,_____,____ all destabilize α helix if close together
–Two aromatic residues are often found
–The identity of residues near the end of the helix segment can affect the
-An α helix is not formed due to strong repulsion of adjacent Glu residues for a long block of Glu residues at pH 7
-Lys and Arg are positive at pH7 and do not form α helix
-Bulk and shape of Asn, Ser, Thr, Cys all destabilize α helix if close together
-Two aromatic residues are often found 3 residues away from each other resulting in a hydrophobic interaction
-The identity of residues near the end of the helix segment can affect the stability of an α helix.
The Helix Dipole
–Recall that the peptide bond has a strong
-All peptide bonds in the α helix have a
–The α helix has a large
-Negatively charged residues often occur near the
-Recall that the peptide bond has a strong dipole moment
–Carbonyl O negative
–Amide H positive
-All peptide bonds in the α helix have a similar orientation
-The α helix has a large macroscopic dipole moment
-Negatively charged residues often occur near the positive end of the helix dipole
Helix dipole. The electric dipole of a peptide bond is transmitted along
AA (-) often found near
Helix dipole. The electric dipole of a peptide bond is transmitted along an α-helical segment through the intrachain hydrogen bonds, resulting in an overall helix dipole. In this illustration, the amino and carbonyl constituents of each peptide bond are indicated by + and – symbols, respectively. Non-hydrogen-bonded amino and carbonyl constituents of the peptide bonds near each end of the α-helical region are shown in red.
AA (-) often found near N-terminus of the helical segment, AA (+) usually at C-terminus.
β Sheets (or β pleated Sheets)
-The planarity of the peptide bond and tetrahedral geometry of the α-carbon create a
-Sheet-like arrangement of backbone is held together by
-Side chains protrude from the sheet alternating in
-The planarity of the peptide bond and tetrahedral geometry of the α-carbon create a pleated sheet-like structure (zigzag)
-Sheet-like arrangement of backbone is held together by hydrogen bonds between the backbone amides in different strands
-Side chains protrude from the sheet alternating in up and down direction
Parallel and Antiparallel β Sheets
-Parallel or antiparallel orientation of two chains within a sheet are possible
-In parallel β sheets the H-bonded strands run in the same direction
—Resulting in bent H-bonds (weaker)
-In antiparallel β sheets the H-bonded strands run in opposite directions
-Resulting in linear H-bonds (stronger)
β Turns
-β turns occur frequently whenever
-The 180°turn is accomplished over
–The turn is stabilized by a
-Proline in position
–β turns are often found near the surface of a
-β turns occur frequently whenever strands in β sheets change the direction
-The 180°turn is accomplished over four amino acids
-The turn is stabilized by a hydrogen bond from a carbonyl oxygen to amide proton three residues down the sequence
-Proline in position 2 or glycine in position 3 are common in β turns
-β turns are often found near the surface of a protein, where the central two AAs can H-bond with water
Most common types of beta turns
Type I and type II β turns are most common; type I turns occur more than twice as frequently as type II. Type II β turns usually have Gly as the third residue. Note the H-bond between the peptide groups of the first and fourth residues of the bends.
Proline Isomers
-Most peptide bonds not involving proline are in the trans configuration (>99.95%)
-For peptide bonds involving proline, about 6% are in the cis configuration. Most of this 6% involve β-turns
-Proline isomerization is catalyzed by proline isomerases
Circular Dichroism (CD) Analysis
-CD measures the
-Chromophores in the chiral environment produce
-CD signals from peptide bonds depend on
-CD measures the molar absorption difference Δε of left- and right-circularly polarized light: Δε = εL – εR
-Chromophores in the chiral environment produce characteristic signals
-CD signals from peptide bonds depend on the chain conformation
-can only determine secondary structure not tertiary structure
Protein Tertiary Structure
-Tertiary structure refers to the
-Stabilized by numerous
-Interacting amino acids are not necessarily
-Two major classes
Tertiary structure refers to the overall spatial arrangement of atoms in a protein
Stabilized by numerous weak interactions between amino acid side chains.
–Largely hydrophobic and polar interactions
–Can be stabilized by disulfide bonds
Interacting amino acids are not necessarily next to each other in the primary sequence.
Two major classes
Fibrous and globular (water or lipid soluble)
