CHAPTER 4 Flashcards
(133 cards)
1
Q
Many conformations are possible for proteins, due to what?
A
Due to flexibility of amino acids linked by peptide bonds
2
Q
some proteins make diseases from wrong folding
A
true
3
Q
At least one major conformations has biological activity, and hence is considered the protein’s
has the lowest ΔG°
A
native conformation
4
Q
indicates the thermodynamic favorability of a physical or chemical process
lesser = better favorability
A
ΔG°
5
Q
driving force of protein folding
A
INTRA molecular and INTER molecualr forces
6
Q
Levels of Protein Structure
A
1°structure
2°structure
3˚ structure
4˚ structure
7
Q
Levels of Protein Structure
the sequence of amino acids in a polypeptide chain, read from the N-terminal end to the C-terminal end
A
1°structure
8
Q
Levels of Protein Structure
the ordered 3-dimensional arrangements (conformations) in localized regions of a polypeptide chain; refers only to interactions of the peptide backbone
interaction of 2 chains
A
2°structure
9
Q
2°structure examples
A
a-helix and b-pleated sheet
10
Q
Levels of Protein Structure
3-D arrangement of all atoms
A
3˚ structure
11
Q
Levels of Protein Structure
arrangement of monomer subunits with respect to each other
A
4˚ structure
12
Q
what type of sequence of proteins determines its 3-D conformation
A
1˚ Structure
13
Q
Changes in just one amino acid in sequence can alter biological function
A
true
14
Q
amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another
A
peptide bond
15
Q
what bond is present in the interactions of these proteins:
2°structure
3˚ structure
4˚ structure
A
Intermolecular Forces of Attraction (IMFA)
16
Q
structure of proteins where it is the hydrogen bonded arrangement of backbone of the protein
A
2˚ Structure
17
Q
Two bonds have free rotation:
angles that determine the conformation of a polypeptide chain
A
phi bond and psi bond
18
Q
Bond between a-carbon and amino nitrogen in residue
A
phi bond φ
19
Q
Bond between the a carbon and carboxyl carbon of residue
A
psi bond ψ
20
Q
what direction is the Coil of the helix
A
clockwise or right-handed
21
Q
There are _________ amino acids per turn in an a-Helix
A
3.6
22
Q
Repeat distance of an a-helix is
A
5.4Å
23
Q
in an a-Helix protein, each peptide bond is _________ and __________
A
s-trans and planar
24
Q
in an a-Helix protein, C=O of each peptide bond is hydrogen bonded to the N-H of the _______ amino acid away, which makes the hydrogen bond of the carboxyl and N-H parallel
A
fourth
25
why does proline disrupt an a-helix
creates a bend
the restricted rotation due to its cyclic structure and (2) its a-amino group has no N-H for hydrogen bonding
26
amino acid with strong electrostatic repulsion that disrupt an a-helix, caused by the proximity of several side chains of like charge
(basic) Lys and Arg or (acidic) Glu and Asp
27
amino acid with steric crowding caused by the proximity of bulky side chains that disrupt an a-helix
Val, Ile, Thr
28
Polypeptide chains lie adjacent to one another; may be parallel or antiparallel
R groups alternate, first above and then below plane
peptide bond is s-trans and planar
b-Pleated Sheet
29
b-Pleated Sheet's C=O and N-H are _______to axis of the sheet
perpendicular
30
C=O---H-N hydrogen bonds are between _________ sheets and ________ to the direction of the sheet
adjacent and perpendicular
31
what happens with parallel chains in b-Pleated Sheet
weakens the sheet and makes the chains diagonal hydrogen bonds (>=< 120)
32
what happens with parallel chains in anti parallel b-Pleated Sheet
stronger due to the 180 degree hydrogen bonds
33
a common non-repetitive irregular 2˚ motif in anti-parallel structure
b-bulge
34
b-bulge is mainly due to
a bulky r group
35
also known as beta turns or hairpin turns, are a type of secondary structure in proteins. They are irregular structures that cause a reversal in the peptide backbone. Reverse turns consist of four amino acid residues in a non-helical segment,
used when Polypeptide changes direction
Reverse turns
36
Reverse Turns usual amino acids
Glycine, Proline
37
why are Glycine, Proline seen in Reverse Turns
offers flexibility
38
the combination of a- and b-sections in s structure
Supersecondary structures
39
Supersecondary structures
two parallel strands of b-sheet connected by a stretch of a-helix
bab unit
40
Supersecondary structures
two antiparallel a-helices
aa unit
41
Supersecondary structures
an antiparallel sheet formed by a series of tight reverse turns connecting stretches of a polypeptide chain
b meander
42
Supersecondary structures
a repetitive supersecondary structure formed when an antiparallel sheet doubles back on itself
greek key
43
Supersecondary structures
created when b-sheets are extensive enough to fold back on themselves
b barrel
44
Supersecondary structures components
linker, a-helix or b-sheet
45
A linked series of _______. This arrangement occurs in the protein rubredoxin from Clostridium pasteurianum.
b-meanders
46
The Greek key pattern in a b-meanders barrel occurs in
human prealbumin
47
A b-barrel involving alternating ________. This arrangement occurs in triose phosphate isomerase from chicken muscle
bab units
48
Top and side views of the polypeptide backbone arrangement in triose phosphate isomerase. Note that the a-helical sections lie ________ the actual b-barrel
outside
49
is a protein found in connective tissue, skin, tendon, bone, and cartilage.
Collagen
50
Collagen consists of three polypeptide chains wrapped around each other in a ropelike twist to form a triple helix called _________; MW approx. 300,000
tropocollagen
51
in collagen, 30% of amino acids in each chain are ____________; hydroxylysine also occurs
Pro and Hyp (hydroxyproline)
52
in collagen, Every third position is __
Gly
53
in collagen, Each polypeptide chain is a helix but not an a helix
true
54
in collagen, The three strands are held together by hydrogen bonding involving
hydroxyproline and hydroxylysine
55
with age, collagen helices tend to become more cross-linked due to the formation of covalent bonds between____________, which contributes to the reduced elasticity and increased stiffness of tissues like skin and cartilage as we get older
lysine (Lys) and histidine (His) residues
56
contain polypeptide chains organized approximately parallel along a single axis.
They consist of long fibers or large sheets
tend to be mechanically strong
are insoluble in water and dilute salt solutions
important structural roles in nature
Fibrous proteins
57
Fibrous proteins examples
keratin
collagen of connective tissue of animals including cartilage, bones, teeth, skin, and blood vessels
58
proteins which are folded to a more or less spherical shape, tertiary level
they tend to be soluble in water and salt solutions
nearly all have substantial sections of a-helix and b sheet
Globular Proteins
59
In Globular proteins, where are the polar side chains and nonpolar side chains
most of their polar side chains are on the outside and interact with the aqueous environment by hydrogen bonding and ion-dipole interactions
most of their nonpolar side chains are buried inside
60
Comparison of Shapes of Fibrous and Globular Proteins
Fibrous proteins are generally composed of long and narrow strands and have a structural role (they are something) Globular proteins generally have a more compact and rounded shape
61
The 3-dimensional arrangement of atoms in the molecule.
Interactions between side chains also plays a role
3˚ Structure of Proteins
62
3˚ Structure of Proteins example
fibrous protein
globular protein
63
3˚ Structure of Proteins
backbone of protein does not fall back on itself, it is important aspect of 3˚ not specified by 2˚ structure.
fibrous protein
64
3˚ Structure of Proteins
more information needed. 3k structure allows for the determination of the way helical and pleated-sheet sections fold back on each other.
globular protein
65
in the context of protein folding refers to a three-dimensional structure determined using a technique called "crystallography," which allows scientists to precisely visualize how helical and pleated-sheet sections
3K structure
66
Forces Involved in 3˚ Structure
Noncovalent interactions: hydrogen bonding between polar side chains
hydrophobic interaction between nonpolar side
electrostatic attraction and repulsion
Covalent interactions: Disulfide (-S-S-) bonds between side chains of cysteines
67
Forces that stabilize the tertiary structure of proteins
the process where a metal ion binds to specific amino acid side chains within a protein molecule
Metal ion coordination
68
Forces that stabilize the tertiary structure of proteins
refer to the non-polar, "water-fearing" amino acid side chains within a protein molecule tending to cluster together in the protein's interior,
Hydrophobic interactions
69
Forces that stabilize the tertiary structure of proteins
a covalent bond that forms between two cysteine amino acids in a protein
disulfide bond
70
Forces that stabilize the tertiary structure of proteins
bonds between polar amino acid side chains and other parts of the protein. These bonds are important for stabilizing the protein's secondary structure
Side chain hydrogen bonds
71
Forces that stabilize the tertiary structure of proteins
the attractive force between oppositely charged amino acid side chains within a protein molecule
may also be repulsion from same charges
Electrostatic attraction
72
the arrangement in space of all atoms in a polypeptide chain
Tertiary (3 ° ) structure
73
it is not always possible to draw a clear distinction between 2°and 3°structure
true
74
the association of polypeptide chains into aggregations
Quaternary (4 ° ) structure
75
uses a perfect crystal; that is, one in which all individual protein molecules have the same 3D structure and orientation
exposure to a beam of x-rays gives a series diffraction patterns
X-ray crystallography
76
X-ray crystallography information on molecular coordinates is extracted by a mathematical analysis called a
Fourier series
77
Determination of 3°Structure
can be done on protein samples in aqueous solution
2-D Nuclear magnetic resonance
78
* A single polypeptide chain of 153 amino acids
* A single heme group in a hydrophobic pocket
* Most polar side chains are on the surface
* Nonpolar side chains are folded to the interior
*has a coordination covalent bond
*stores oxygen
Myoglobin
79
Myoglobin
* regions of a-helix; regions of b-sheet
8 and no
80
Myoglobin
* Two His side chains are in the __________, involved with interaction with the heme group
interior
81
Myoglobin
* Fe(II) of heme has 6 coordinates sites;
4 interact with N atoms of heme, 1 with N of a His side chain, and 1 with either an O2 molecule or an N of the second His side chain
82
Noncovalent interactions that stabilize proteins are
weak and can be disrupted
83
the loss of 3˚ structural order…”Unfolding”
Denaturation:
84
Denaturation can be brought about by:
* heat
* large changes in pH, which alter charges on side chains, e.g., -COO- to -COOH or -NH3+ to -NH2
* detergents such as sodium dodecyl sulfate (SDS) which disrupt hydrophobic interactions
* urea or guanidine, which disrupt hydrogen bonding
*mercaptoethanol, which reduces disulfide bonds
85
____ and ___ can bind to the Heme group of Myoglobin
O2 and CO
86
Factors Causing Denaturation
1. change in pH
2. heating
3. chaotropic agents
4. detergents
5. reducing agents
6. varying salt concentration
7. heavy metal ions
8. non-polar solvents
87
does denaturation involve cutting of bonds?
no
88
Factors Causing Denaturation
protonation of proteins
destroys H-bonds
affects electrostatic interactions
Addition of an Acid
6M HCl (pH 2)
89
Factors Causing Denaturation
deprotonation of proteins
destroys H-bonds
affects electrostatic interactions
Addition of a Base
6M NaOH (pH 10)
90
Factors Causing Denaturation
↑molecular interactions
destroys weak interactions (H-bonds, ionic bonds and hydrophobic interactions)
can irreversibly denature proteins through
deamination of asparagine and glutamine or hydrolysis of peptide bonds
Heating
<60
91
Factors Causing Denaturation
prevents protein to fold back to its original structure after temperature denaturation
Flash Freezing
92
Factors Causing Denaturation
salt ions bind to protein’s ionizable groups
decrease interactions between oppositely charged groups
water molecules can then form solvation spheres around these groups
Change in Salt Concentration
6M NaCl
93
Factors Causing Denaturation
substances that enhance the solubility of non-polar compounds in water by disordering water molecules
H-bonders that destroy the regular water structure
destruction of water structure increases the hydrophobic effect thus promotes the unfolding and dissociation of protein molecules
Chaotropic Agents
8M Urea
94
Factors Causing Denaturation
amphipatic
cause proteins to unfold into extended polypeptide chains
hydrophobic tail denatures protein by penetrating the protein’s interior and disrupting the hydrophobic
interaction
Detergents
1% Sodium Dodecyl Sulfate (SDS)
95
Factors Causing Denaturation
converts disulfide bridges to sulfhydril groups
the only denaturant that cleaves covalent bonds
Reducing Agents
β-mercaptoethanol
96
Factors Causing Denaturation
disrupt salt bridges by forming ionic bonds with negatively charged groups
bonds w/ -SH groups that results in significant changes in protein structure and function
Heavy Metal Ions
97
Factors Causing Denaturation
interacts w/ non-polar R groups
interfere w/ hydrophobic interactions
Non-polar solvents
98
a series of experiments that demonstrated that a protein's amino acid sequence determines its three-dimensional structure.
The primary sequence of a protein contains all the information needed to direct the protein's folding into its native state.
proteins can go back to its native state, but the order of is important
Anfinsen’s Experiment
99
the association of polypepetide monomers into multisubunit proteins.
Quaternary (4 ° ) structure
100
Quaternary (4 ° ) structure
Some common multi-subunits include
* dimers
* trimers
* tetramers
101
Quaternary (4 ° ) structure
Noncovalent interactions
electrostatics, hydrogen bonds, hydrophobic
102
chart Oxygen-Binding to Hb vs. Mb
hb - sigmoidal
myoglobin - exponential
103
A hetero tetramer of two a-chains (141 amino acids each) and two b-chains (153 amino acids each); a2b2
Each chain has 1 heme group; can bind up to 4 molecules of O2
transport oxygen
Characteristic of allosteric behavior
Structural changes occur during binding of small molecules
Oxygen Binding of Hemoglobin
104
In hemoglobin, Binding of O2 exhibited by _________; when one O2 is bound, it becomes easier for the next O2 to bind
positive cooperativity
105
The structure of oxygenated Hb is different from that of unoxygenated Hb
true
106
basically stating that it gives away oxygen at environments with lower oxygen concentrations
refers to the phenomenon where hemoglobin's affinity for oxygen decreases in a more acidic environment (lower pH), causing it to release more oxygen to tissues that are metabolically active and producing more carbon dioxide, which lowers the pH
The Bohr Effect
107
A Summary of the Bohr Effect in lungs vs Actively Metabolizing Muscle
lungs
Higher pH than actively metabolizing tissue
Hemoglobin binds O2
Hemoglobin releases H+
Actively Metabolizing Muscle
Lower pH due to production of H+
Hemoglobin releases O2
Hemoglobin binds H+
108
A comparison of the oxygen-binding properties of hemoglobin in the presence and absence of BPG
the presence of the BPG markedly decreases the affinity of hemoglobin for oxygen.
109
Hemoglobin in blood is also bound to another ligand, with drastic effects on its oxygen-binding capacity
2,3-bisphosphoglycerate
110
A comparison of the oxygen-binding capacity of fetal and maternal hemoglobins.
Fetal hemoglobin binds less strongly to BPG and, consequently, has a greater affinity for oxygen than does maternal hemoglobin.
111
sickness due to mutation in the beta-chains
anemia
112
Sickle cell genes help to acquire immunity against _________in early childhood
malaria
113
prompts the bone marrow to manufacture fetal hemoglobin (Hb F), which does not have b-chains, instead it has γ chains
medication primarily used to treat sickle cell disease by increasing the production of fetal hemoglobin (HbF), which helps keep red blood cells round and flexible, thereby reducing the frequency and severity of pain crises associated with sickle cell anemia
Hydroxyurea
114
Can 3˚ structure of protein be predicted?
Yes, within limitations
115
The integration of biochemistry and computing has led to
Protein structure prediction is one of the principal application
bioinformatics
116
First step to predict protein structure is to search for
sequence homology
117
Refers to similarity of two or more sequences
Homology
118
Hydrophobic interactions are major factors in protein folding
true
119
occurs so that nonpolar hydrophobic side chains tend to be on inside away from water, and polar side chains on outside accessible to aqueous environment
Folding
120
Hydrophobic interactions are _______
spontaneous
121
small, spherical vesicles made of lipids that can carry drugs and other molecules to specific areas of the body
liposomes
122
liposomes components
inner aqueous compartment
hydrophilic surfaces
hyphobic tails (sandswiched in hydrophilic surfaces)
123
Hydrophobic and Hydrophilic Interactions in Proteins
hydrophobic side chains go inside and hydrophilic go outside
124
when they mix to form a solution, the overall entropy of the system decreases, which is considered thermodynamically unfavorable because the natural tendency is for systems to move towards increased disorder (higher entropy); this typically happens when the solute molecules become highly ordered or structured upon dissolving in the solvent, reducing the system's overall randomness.
Therefore, nonpolar substances do not dissolve in water; rather, nonpolar molecules associate with one another by hydrophobic interactions and are excluded from water.
Unfavorable entropy
125
Proteins that do not fold correctly may interact with other proteins in an undesired manner and aggregates may result
true
126
In the protein-dense environment of a cell, proteins may begin to fold incorrectly or may associate with other proteins before folding is completed
Special proteins called __________ aid in the correct and timely folding of many proteins
exist in organisms from prokaryotes to humans
Protein Folding Chaperones
127
were the first chaperone proteins discovered
hsp70
128
how do chaperonins guide a protein?
chaperonins have a a cap and cylinder where the protein goes in
once a protein goes in, it deals it with a cap and causes the cylinder to change shape and create a hydrophilic environemnt for the folding
cap comes off to release the protein
129
Balancing The Components of Hb
the a- and b-globin genes are on different chromosomes. Excess a-chain is produced. If excess a-chains can interact, they form aggregates called a-inclusion bodies that damage red blood cells. The globin chaperone (AHSP) binds to a-globin and both keeps it from aggregating with itself and delivers it to the b-globin so that the a-globin and b-globin can bind together to form the active tetramer.
130
is an inherited blood disorder in which the body doesn't make as much beta globin as it should.
Complications may include delayed growth, bone problems causing facial changes, liver and gall bladder problems, enlarged spleen, enlarged kidneys, diabetes, hypothyroidism, and heart problems.
Beta thalassemia
131
transmissible, untreatable, and fatal brain diseases of mammals
Prion diseases
132
Prion diseases examples
* mad-cow disease (bovine spongiform encephalopathy or BSE)
* scrapie in sheep
* chronic wasting disease (CWD) in deer and elk
* human spongiform encephalopathy (kuru and Creutzfeldt Jakob disease) in humans
133
a small (28-kDa) protein
a natural glycoproteins found in the cell membranes of nerve tissue
prion
