Biochem Protein Lecture 6 Flashcards
Beta Sheets are not covered on the next exam
Protein ___ can be described as the spatial arrangement of atoms in a protein
Conformation
These changes achieve spatial arrangements without breaking covalent bonds
Conformational changes
There are 100s of theoretical conformations possible. Do most of them predominate?
No, one or a few underbiological conditions predominate
A few stable conformations under a given set of conditions are necessary because some conformational changes must take place in proteins as they bind to other molecules
Those conformation which occur are the ones that are thermodynamically
Most stable (lows Gibbs free energy)
The actual resonance structure of peptide bonds is a hydrid of the two resonance forms. How much does the resonance stabilize the peptide bond?
The six atoms of the peptide group lie in a single plane with the O atom of the carbonyl group and the H atom of the amide N trans to each other
Are the peptide C-N bonds able to rotate freely? Why or why not?
21kcal//mol
No
Partial double bond character
Can rotation occur about N-Cα and Cα-C bonds?
Are cis and trans peptide bond formations possible?
What form are the peptides in proteins? Why?
What is the exception?
Yes (Look at diagrams)
Yes
Trans
There is less steric interference between the R groups of adjacent aa
X-Pro sequence, X can be any other aa and cis conformation is favored
These are proteins in a functional, folded conformation
The tendency to maintain this conformation is
Native Proteins
Stability
Is the native conformation of proteins very stable or slightly?
What stabilizes native conformation?
Slightly (20-65kJ/mole)
Disulfide bonds
Weak, noncovalent interactions (H-bonding, hydrophobic interactions and ionic interactions)
What range of energy is require to break a single covalent bond?
What range is required to disrupt weak interactions?
200-460 kJ/mol
4-30kJ/mol
If weak interactions are so much weaker than strong, why do they predominate at stabilizing structure?
Therefore, the protein with the lowest or highest G is the one with the greatest number of weak interactions?
There are many of them
Lowest G
When water surrounds a hydrophobic molecule, a highly structured cell of water forms called
Solvation layer
Entropy actually increases or decreases with a solvation layer? Why?
Increases
Hydrophobic groups cluster together and only part of their surface exposed to surface.?
_____ Interactions are very important in stabilizing protein conformations
Hydrophobic
When hydrophobic residues are buried in the protein interior away from water, what does that do to the number of H-bonds and ionic interactions within the protein?
Maximizes them
This bond also makes an important contribution to protein conformation
How many bonds separate the alpha carbons of adjactent aa residues in a protein?
Peptide Bond
3 covalent bonds
What did X-ray diffraction studies off aas, dipeptides and tripeptides reveal regarding bond length of C-N in each structure?
The C-N peptide bond is shorter than the C-N bond in a simple amine
Atoms associated with peptide bonds are
Coplanar
The bond angles of the alpha carbon atoms correspond to ____ hydrid orbitals
sp3
The 3σ bonds associated with each of the carbonyl C and N atoms involve ______ hybrid orbitals. The axes are planar, and the bond angles are ______ degrees
sp2
120 degrees
The C-N peptide bond distance is in between C-N single and double bonds.
Can partial C-N double bonds rotate?
!
No.
Why is there a shorter bond in peptide bonds?
Due to resonance or partial sharing of 2 pairs of electrons between carbonyl oxygen and amide nitrogen.. A small dipole results
Be able to draw the hybrid of the two resonance forms of peptide bonds.
How much does the resonance stabilize the peptide bond in kcal/mol
The six atoms of the peptide group lie in a single plane with the atom of the carbonyl group and the H atom of the aminde N _____ to each other
Slide 10.
21 kcal/mole
trans
Is rotation permitted about N-C alpha and C-C alpha bonds?
Yes. Even though the arrangement of atoms in the peptide bond is planar and rotation about the peptide bond is restricted, cis and trans peptide bond conformations are possible
The peptide in proteins is in the _____ form because there is less steric interference between the R groups of adjacent aa
What is the exception?
Trans
Proline, favors cis because of ring.
In terms of protein conformations, rotation about the single bonds to the ________ results in a range of protein conformation
Alpha carbon
Bond angles from rotation about the N-Cα are labeled _____ and for rotation about the Cα-C theyre___
Bond angles from rotation about the N-Cα are labeled φ (phi) and for rotation about the Cα-C they’re labeled ψ (psi)
Study positive and negative rotation (slide 14)
!
Allowed values for ψ and φ are graphically shown in a
Ramachandran Plot
What do the darkly shaded areas of Ramachandran Plots reflect?
What about moderately shaded regions?
What about the lightly shaded regions?
What about the yellow regions?
Fully allowed conformations
Conformations allowed at the extreme limits for unfavorable atomic contacts
Permissible conformations if a little flexibility is allowed in the bond angles
Not allowed
This term refers to the local conformation of some part of a polypeptide
Common, regular folding patterns of polypetide backbones include
The simplest arrangement a polypeptide can assume it a
Secondary Structure
Alpha helix and Beta conformations
Helical Structure
If the Al ψ and φ angles are constant throuhghout a polypeptide chain, the polypeptide will have a
Helical shape
The given set of angles of ψ and φ determine the type of helix
What protrudes out from the helical backbone of polypetide helical structures?
R-groups
For the α polypeptide helix the repeating unit is a single turn of the helix which extends ______ A along the long axis
Each helical turn is ____ aa residues
What are the aa residue conformations with φ and ψ?
Is it right or left handed?
- 4 A
- 6 residues
φ = - 60°
ψ = - 45 to - 50°
Right handed
What percent of all aa resiudes in polypeptides are α-helices?
What do internal (intrachain) H-bonds do to the α-helix?
Where are the H bonds in fig 4.4a?
1/4
Stabilize
H bonded to N of peptide linkage and carbonyl oxygen of fourth aa on the amino-terminal side chain of the peptide bond
With the α helix, every peptide bond except those close to the helix participates in
All H bonds combined impart lots of ___ to the helical structure
H-bonding (?)
Stability
Can the alpha helix form with both D and L amino acids at the same time?
Can the naturally occurring L -amino acids form right and left handed helices?
No, it must be all L or all D
Yes, they can form both
Which helix formed by L-amino acids is less stable and has not been observed in proteins?
Left handed
In defined helices, this is the distance parallel to axis in which the helix makes one turn
Pitch (p)
In defined helices, the distance parallel to the axis from one residue to the next is the
Rise (h)
In defined helices, the number of amino acid residues is
n
In defined helices, this is the distance parallel to the axis in which the structure directly repeats itself. It contains an integral (m) number of polymer residues
Repeat
The number of polymer residues is m
Is the α-helix one of the idealized helices?
Why is it 3.6 residues per turn?
What is the rise of the α-helix?
What is the pitch?
No.
It repeats after 18 residues, which amounts to 5 turns
1.5 A/resiude
p=nh, p=3.6*1.5 = 5.4 A
In the alpha helix, if we include the H bond, a loop of ___ atoms is formed
13
Polypeptide helices are described as nN helices where
this is the number of residues per turn
this is the number of atoms in the hydrogen bonded loop
So what are the values for the α helix?
n
N
n=3.6 N = 13
How much is each successive turn of the αhelix bonded to adjacent turns, resulting in significant structural stability?
3-4 H-bonds
What are the two other possible helical structures of polypeptide chains?
3(10) helix
π helix
This other helix is observed in some proteins, and is less common the α helix. It is right handed, and frequently found within α helical proteins
What is an example of an α helical protein it is found in?
3(10) helix
myoglobin
how many atoms are in the H loop of a 3(10) helix?
10 (duh)
Which other helix is not observed in proteins? It has 16 atoms in the H loop with 4.4 residues/turn
π helix
If a polypeptide had all of its residues in a particular secondary structure, like α helix, the points for all residues would
Many values of φ and ψ are prohibited by _____ between atoms in the polypeptide backbone and AA side chains
Superimpose
Steric interference
The AA residues in this helix have φ and ψ conformations of ψ = -45 to -50 and φ = -57 to -60
In contrast, this helix results from φ and ψ conformations of -49 and -26, respectively
α helix
3(10) helix
Ramachandran has calculated the distances between atoms in a ________ for all sets of φ and ψ angles. He wanted to determine which angles are sterically forbidden based on distances less than the sume of the van der Waals radii of the atoms
Tripeptide of L-ala
No two atoms should approach each other more closely than is allowed by their
van der Waals radii
You might have to know minimum contact distances between atoms and which angles are allowed. Ask the prof
!
Is the Ramachandran plot symmetric?
What does this mean?
No
left and right handed helical regions have different areas of stability
What is the fact that left and right handed helical regions have different areas of stability a consequence of?
All AAs are in the L form
Steric interference between the side chains and the backbone of the helix is less with a ___ handed helix
What could affect the allowed regions even more?
Right handed
Bulkier or less bulky (gly) AAs.
Are β-sheet structures of polypeptide chains found?
Yes
Not all polypeptides can form an α helix. What five things prevent it from occurring
1) A long block of glu residues
20 Many adjacent lys/arg residues
3) Asn, ser, thr, and cys residues that are close together
4) Pro and gly are part of the polypeptide chain
5) Identity of aa residues near the α helical segment
Why does A long block of glu residues prevent alpha helices?
There can be no alpha helix at pH 7 because of negative charges repelling one another
Why do many adjacent lys/arg residues prevent the formation of an alpha helix
There can be no alpha helix at pH 7 due to positive charges repelling one another
Why do Asn, ser, thr, and cys residues that are close together prevent the formation of an alpha helix
They are bulky and their shape
The twist of an alpha helix insures critical interactions between aa side chains _______ residues away from each other
3-4 residues away from each other
Why are pro and gly rarely found in alpha helices?
N is part of a rigid ring in pro, so rotation about N-C α bond is not possible, which introduces a kink in an α helix. There is also no H on N for H bonding
Gly has a lot of conformation flexibility resulting in coiled structure
Why can the identity of aa residues near the end of a polypeptide chain prevent the stability of an alpha helix?
A small dipole exists in each peptide bond. Net dipole increases with helix length. The four aa at each end of the helix do not participate fully in helix H bonds. Neg. charged aa found near the amino terminus (STABILIZE + CHARGE). Positively charged aa found near the carboxy terminus
