Week 1 Protein Structure and Function
A basic residue with pH = pKa, will have what net charge?
+0.5
A basic residue with pH >> pKa will have what charge?
0
An acidic residue with pH less than pKa will have what charge?
0
Protein backbone conformations are constrained by what property of the peptide bond?
Partial double-bond character of the amide bond; this keeps 6 atoms in a plane
proline in the middle of an alphahelix can introduce a
kink
amino acid with a secondary amine group
proline
A basic residue with pH << pKa will have what charge?
+1
An acidic residue with pH = pKa will have what net charge?
-0.5
An acidic residue with pH >> pKa will have what charge?
-1
Peptide bonds are what type of chemical bond
Amide
Primary structure is determined by what type of bonding?
Covalent
acidic amino acids
Glutamate, aspartate
Secondary structure is principally determined by what bonding?
Hydrogen bonding between backbone atoms (nitrogenhydrogens and carbonyl oxygens.
What types of forces hold together quaternary structures
Hydrophobic (most important), side-chain hydrogen bonding, disulfide bonds, ionic bonds, van der Waals.
What types of forces hold together tertiary structure?
Hydrophobic (most important), side-chain hydrogen bonding, disulfide bonds, ionic bonds, van der Waals.
basic amino acids
Lysine, arginine, histidine
Which amino acid can be a methyl donor
Methionine
aromatic amino acids
Phenylalanine, tyrosine, tryptophan, histidine
three common post-translational modifications:
Phosphorylation (Ser, Thr, Tyr) hydroxylation (Pro) Carboxylation (Glu) Glycosylation (Asn, Ser, Thr) acetylation (His, Lys) methylation (Lys).
Proline
R-group folds back and is covalently attached to the nitrogen of the amino acid. This greatly constrains the structure and it is inconsistent with the regular pattern of an alpha-helix
What is the structure found uniquely in collagen?
Triple helix
Name the BCAAs
Valine, leucine, isoleucine
Which of the following proteins does not have a quaternary structure? A. Myoglobin B. Hemoglobin C. IgG D. Superoxide dismutase E. Collagen
a
To increase the solubility of a protein, you need to change
a hydrophobic amino acid to one that is more polar.
Beta-secretase
a protein responsible for maturing A-beta, the protein responsible for forming amyloid plaques.
Secondary structures such as
alpha helices and beta-sheets satisfy all the possible main-chain hydrogen bonding capacity
Aromatic residues tend to be more hydrophobic than
any of the polar residues.
What is the smallest amino acid? A. Lysine B. Glycine C. Alanine D. Serine E. Proline
b
Which of the following amino acid R-groups, shown within a protein sequence, is the most likely to be found on the interior of a protein? A. Aspartate B. Isoleucine C. Glutamine D. Lysine
b
Methionine is also hydrophobic, but less so than isoleucine
because of the more polar sulfur atom in the chain.
Aromatic residues tend to be less hydrophobic than the
branched chain amino acids
1. Which of the following component of a water-soluble globular protein that is more likely to be present in the center of the molecule rather than on its surface? A. A glutamate side chain B. A histidine side chain C. A phenylalanine side chain D. A phosphate group covalently linked to a serine side chain E. An oligosaccharide covalently linked to an asparagine side chain
c
Disulfide bonds stabilize principally this type of structure in proteins. A. Primary B. Secondary C. Tertiary D. Quaternary E. Macromolecular Assembly
c
Imidazole is the name of the side chain on histidine, and can be used as a buffer by itself. It has a pKa of 7.2. At which of the following pH values will this buffer best? A. 5 B. 6 C. 7 D. 8 E. 9
c
Use the Henderson Hasselbalch equation to determine the pH of a solution containing 5 mM acetic acid [AH] and 10 mM sodium acetate [A- ]. The pK of acetic acid is 4.75. A. 4.0 B. 4.45 C. 5.05 D. 5.55 E. 6.0
c
Your grandmother has become increasingly forgetful during the past 2 years. Last week she actually got lost on the way back from the grocery store a few blocks down the road. One treatment that could perhaps help her would be a drug that does which of the following? A. Reduces the synthesis of transthyretin B. Reduces the formation of immunoglobulins C. Inhibits the activity of β-secretase D. Reduces the formation of α-synuclein E. Adds phosphate groups to tau protein
c Beta-secretase is a protein responsible for maturing A-beta, the protein responsible for forming amyloid plaques
Porins contain what type of characteristic domain structure? A. Transmembrane alpha helix B. 7-transmembrane helical structure C. IgG fold D. Beta-barrel E. Globin fold
d
Which amino acid is considered a helical breaker? A. Alanine B. Glycine C. Phenylalanine D. Proline E. Methionine
d
Which amino acid(s) are sulfur containing? A. Just Cysteine B. Serine and Threonine C. Methionine and Threonine D. Cysteine and Methionine E. Arginine and Lysine
d
Which of the following amino acid side chains is the most hydrophobic? A. Methionine B. Tyrosine C. Tryptophan D. Isoleucine E. Alanine
d
Ionic bonds occur in proteins where and how often? A. They constitute a major stabilizing force for folding B. They occur often on the surface of proteins C. They occur in all proteins to stabilize their core D. They occur occasionally in the interior of proteins E. Ionic bonds are never found in proteins
d Being close to an opposite charge can stabilize it in the interior of the protein such interactions though, are not always favorable, and sometimes are destabilizing. So, they do occur, but are relatively rare compared to hydrogen bonding interactions and hydrophobic interactions.
A genetic engineer wants to produce athletes with increased hemoglobin concentration in the erythrocytes, to improve oxygen supply to the muscles. To do so, the water solubility of the hemoglobin molecule must be increased. Which of the following amino acid changes on the surface of the hemoglobin molecule is most likely to increase its water solubility? A. Arg → Lys B. Leu → Phe C. Gln → Ser D. Ala → Asn E. Ser → Ala
d To increase the solubility of a protein, you need to change a hydrophobic amino acid to one that is more polar. The choice with the most substantial change in hydrophobicity is D. The others tend to be polar to polar or hydrophobic to hydrophobic or to something less polar.
primary structure is
determined by the amino acid sequence and any subsequent modifications of that structure.
Most secondary structures form to satisfy principally this type of interaction: A. Hydrophobic Interactions B. Van der Waals forces C. Ionic Bonding D. Disulfide bonding E. Hydrogen bonding
e
Proline is often found near
he ends of alpha-helices, and is considered a "helix breaker".
Amino acids that drive protein folding are principally
hydrophobic amino acids
Histidine is much less
hydrophobic than phenylalanine.
Collagen is a triple helix because
it has a lot of glycine and proline
Charged side chains typically prefer an aqueous environment, so on the surface of a protein, they interact with water
not with other charged residues
substance buffers best at its
pKa value
Tyrosine and tryptophan, because of their hydroxyl and nitrogen groups are somewhat less hydrophobic than
phenylalanine.
ionic bonding in proteins
provide specificity for protein-protein interactions or for ligand binding (e.g. ATP is charged and requires counterions when it bind to a protein binding site), or for internal protein folding.
Disulfide bonds tend to form in
secreted proteins and domains external to the cell They can also form more rarely in cytosolic proteins
Myoglobin
simple, single peptide, single domain, protein
key for the peptide bond
the joining of the carbonyl with the amine
A-beta
the protein responsible for forming amyloid plaques.
Histidine
though aromatic, is charged most of the time
cysteine and methionine
two amino acids of the standard 20 that contain sulfur Homocysteine is another; it is not typically part of proteins but does play a role in metabolism.
: Ionic bonds are
two oppositely charged side chains (e.g. lysine and glutamate) in the interior of proteins.
