Week 3: Protein Structures & Examples Flashcards
In free amino acid, carboxyl (-) and amino group (+)
______ at neutral pH
charged
Amino acids without _______ groups on side chains
exist as _______ (“twin ions”)
charged
zwitterions
Zwiterrions are _______ in solutions
electrically neutral
Isoelectric pH (pI) is pH at which molecule has _____
_____ of (+) and (-) charges
no net charge
same number
for most amino acids, pI =
pKa1 (a-carboxyl) + pKa2 (a-amino)/2
amino acids are usually more soluble at ________ than they are at _______ because they have _______ at ______, and the molecules tend to ________. When the molecular charge is zero, the amino acids can _________.
pH extremes
neutral pH
a net charge
repel each other
aggregate more easily.
four levels of protein structure:
primary, secondary, tertiary, and quaternary.
Not all proteins have ______. For example, only proteins with ______ have quaternary structure.
all four levels
multiple polypeptide chains
Amino acids linked by ______
covalent peptide bonds
Primary protein structure (1°) is the ____ in which amino acids are _____
order
covalently linked together
Both ______ and ______ important in primary structure
amino acid content
order
Primary structure helps determine _____, which determines _____
3D conformation
properties
The three-dimensional arrangement of all atoms
Tertiary structure
Sickle cell anemia results from change in ________
_____ mutation
primary structure
Glu -> Val mutation
The order of amino acid residues in the polypeptide chain
Primary structure
The interaction between subunits in proteins that consist of more than one polypeptide chain
Quaternary structure
The hydrogen-bonded arrangement of the polypeptide backbone.
Secondary structure
When a protein is denatured, the interactions that determine _________ are overcome by the presence of the denaturing agent. Only the ______ remains intact.
secondary, tertiary, and any quaternary structures
primary structure
What is the nature of “random” structure in proteins?
three-dimensional features of these parts of the protein are repeated from one molecule to another
Replacement of tryptophan causes the greatest effect on protein structure and function because Tryptophan has the _____ of any of the common amino acids, and it tends to require _____.
largest side chain
a nonpolar environment
Replacements such as Lys -> Arg usually have very little effect on protein structure and function because
Lysine and arginine are both basic amino acids; exchanging one for the other would not affect the side-chain pKa in a significant way.
Glycine is frequently a ________ because its side chain is…
conserved residue
so small that it can fit into spaces that will not accommodate larger ones.
An amino acid is usually more soluble in aqueous solvent at pH extremes than it is at a pH near the isolelectric point of the amino acid. (Note that this does not mean that the amino acid is insoluble at a pH near its pI.) Why?
At pH extremes, the amino acid molecules mostly carry a net charge, thus increasing their solubility in polar solvent.
Based on the pKa values for the 20 amino acids commonly found in proteins, is there any amino acid that could serve as a buffer at pH 6?
Yes, histidine is the amino acid that can act as a buffer at pH 6 because its side chain pKa is very close to 6, meaning it can readily accept or donate protons over the pH range 5-7.
How do the resonance structures of the peptide group contribute to the planar arrangement of this group of atoms?
The two resonance structures give the C-N bond partial double bond character while leaving the C=O bond with partial double bond character.
The pKa values for the α-COOH and α-NH3+ ionizations ________ with changing side group functionality.
vary relatively little
Globular proteins tend to be ______ in the cytosol or extracellular medium, while fibrous proteins tend to _____.
soluble
form insoluble aggregates
Globular proteins often participate in _____, while fibrous proteins are often employed ____.
biochemical reactions,
employed as structural elements regulating cell shape
Globular proteins are _______ in shape, while fibrous proteins ________.
roughly spherical
usually have extended shapes
On average, the relative composition of globular and fibrous protein types are _____
similar.
Globular and fibrous proteins are different in this respect:
Globular and fibrous proteins are similar in this respect:
Differ in: aqueous solubility, biological function, and molecular shape
Similar in: amino acid composition
Proline is often found at places in proteins that are not alpha-helical because…
unlike other amino acids, proline has a fixed angle of rotation around its C(alpha)-N bond. Proline fits well into beta-turns.
Five possible features limit possible protein configurations and conformations:
- Only one of the 20 available amino acids is used at each position along the primary sequence.
- D- or L-amino acids could be used in proteins. Biology chooses to use only the L-steroisomers.
- The partial double bond character of the C=O and C-N bonds in the peptide group restricts the conformations of the amide plane to the cis and trans forms.
- Steric clashes between atoms restrict the possible Ramachandran angles (or conformations) between amide planes.
- The primary structure of a protein determines the protein’s optimum tertiary structure due to the intrinsic restrictions on possible molecular geometries inherent to each amino acid residue.
There are two critical amino acid residues near the heme group in both myoglobin and hemoglobin. These residues are…
His and His
Two histidine residues on either side of the heme group plane play an important role in the binding of O2 to the heme iron atom. One His forms part of the coordination system for the iron. The other His is near the O2-Fe binding site and modulates ligand interactions with the iron atom.
________ is primarily an O2 storage protein. It has a hyperbolic O2 saturation vs. PO2 curve that allows it to bind O2 readily at the low PO2 values found in peripheral tissues.
Myoglobin
______ is primarily an O2 transport protein. It has a sigmoidal O2 saturation vs. PO2 curve that allows it to bind O2 readily at the high PO2 values found in the lungs and to release O2 readily at the low PO2 values found in peripheral tissues.
Hemoglobin
Both myoglobin and hemoglobin are dominated by ________ and both contain ______ with a central iron atom that forms the ________ of the proteins.
α-helical secondary structure
heme groups
O2 binding site(s)
2,3-BPG promotes ____ among the _____.
2,3-BPG causes movements in the _______ to be coordinated.
The amino terminal nitrogens of the two α subunits of hemoglobin interact with the _____ on 2,3-BPG.
cooperativity, subunits of hemoglobin
four subunits of hemoglobin
negative charges
In oxygenated hemoglobin, pKa = 6.6 for the histidine residues at position 146 on the β-chain. In deoxygenated hemoglobin, the pKa of these residues is 8.2. This data indicates that deoxygenated hemoglobin is a _____ acid than oxygenated hemoglobin. This change in the pKa of the histidine residues underlies the Bohr effect in which _____ in the hydrogen ion concentration reduces the affinity of hemoglobin for O2. The binding of H+ to these His residues _____ their interactions with
___ residues via ______.
weaker
an increase
increases
Asp
salt bridges
How does the difference between the β-chain and the γ-chain of hemoglobin explain the differences in oxygen binding between Hb A and Hb F?
The loss of a histidine residue _____ the interaction of fetal hemoglobin with 2,3-bisphosphoglycerate.
The replacement of ____ in fetal hemoglobin reduces the cooperative interactions of fetal hemoglobin subunits as compared to adult hemoglobin subunits.
reduces
His with Ser
Fetal hemoglobin is essential for the survival of placental animals because Hb F has a _____ affinity for O2 at oxygen partial pressures found in the placenta as compared to the oxygen affinity of Hb A. This difference in affinity for O2 allows O2 from the hemoglobin in the _____ to transfer to the hemoglobin in the ____
higher
mother
fetus
Compared to Hb A, Hb F has a higher affinity for oxygen at the PO2 values found in the placenta. Thus, fetal hemoglobin will “steal” O2 from the mother’s hemoglobin, providing the fetus with oxygen.
A prion is a potentially infectious ______ found in multiple forms in _______. It tends to form plaques that destroy the
______ . Prions ____ species
protein
mammals
nervous tissue
are transmissible across
A series of encephalopathies have been found to be caused by prions. In ____, the disease caused by prions is called bovine spongiform encephalopathy, or more commonly mad-cow disease. In _____, the disease is called scrapie. In ____, it is called Creutzfeldt-Jakob disease.
cows
sheep
humans
Several side chains can be coordinated to a _____ ion.
metal
Hydrogen bonding occurs between the _______
side chains of amino acids.
In secondary structure, each amino acid residue has two bonds with _______ designated by _______
Types - ______ arrangements
free rotation, Ramachandran angles
α-helix and β-pleated sheet
Ramachandran Angles:
____ around these bonds
- phi (Φ): bond between the α-carbon and amino nitrogen
- psi (Ψ): bond between α-carbon and carbonyl carbon
Free rotation around these bonds!
α-Helix:
Helical conformation allows for _______ of _______
* _______ bond strength
* ______ conformation
linear alignment, hydrogen bonds
Maximum
Stable
α-Helix:
Each peptide bond is ______
* Coil of helix is _______
trans and planar
clockwise or right-handed
α-Helix
* ____ of each peptide bond H-bonded to ______
C═O
N-H of fourth amino acid residue
α-Helix:
* C═O≡H—N H bonds ______ to helical axis
* All R groups _______ from the helix
parallel
point outward
Factors That Disrupt the α-Helix:
Proline bends the backbone and restricts rotation due to cyclic structure. Results in absence of N—H for H-bonding in α-
amino group.
Strong electrostatic repulsion caused by proximity of
like charges
Steric repulsion caused by proximity of bulky
side chains
Examples of electrostatic repulsion due to like charges in alpha helix:
Adjacent Lys and Arg or Glu and Asp
Examples of steric repulsion due to bulky groups in alpha helix:
Val, Ile, and Thr
________ in alpha helical structures _______ regular nature of helix
Irregularities
break up
The alpha helix is stabilized by _________ to the helix axis within the ______ of a _________.
hydrogen bonds parallel
backbone
single polypeptide chain
The peptide backbone in the ______ is almost completely extended.
beta sheet
