4 - THE THREE-DIMENSIONAL STRUCTURE OF PROTEINS Flashcards
1
Q
one or (at most) a few have a biological activity
three-dimensional shapes of proteins with biological activity
A
Native conformations
2
Q
Many proteins have no obvious regular repeating structure and are thus frequently described as having large segments of “random structure”
A
Random coil
3
Q
The term random is really what and why?
A
Misnomer; because the same nonrepeating structure is found in the native conformation of all molecules of a given protein, and this conformation is needed for its proper function.
4
Q
the order in which the amino acids are covalently linked together
A
Primary structure
5
Q
the arrangement in space of the atoms in the peptide backbone
have repetitive interactions resulting from hydrogen bonding between the amide N-H and the carbonyl groups of the peptide backbone.
A
Secondary structure
6
Q
What are the two different types of secondary structure?
A
- Alpha helix
- Beta pleated sheet arrangements
7
Q
specific clusters of secondary structural motifs in proteins
A
Domains (super-secondary structure)
8
Q
includes the three-dimensional arrangement of all the atoms in the protein, including those in the side chains and in any prosthetic group
A
Tertiary structure
9
Q
portions of proteins that do not consist of amino acids
A
Prosthetic groups
10
Q
the individual parts of a larger molecule (e.g., the individual polypeptide chains that make up a complete protein)
interactions between these is mediated by noncovalent interaction (h-bonds, electrostatic attractions, and hydrophobic bonds
A
Subunits
11
Q
the interaction of several polypeptide chains in a multisubunit protein
A
Quaternary structure
12
Q
The amino acid sequence (the primary structure) of a protein determines its three-dimensional structure, which, in turn, determines its properties. In every protein, the correct three-dimensional structure is needed for correct functioning.
A
13
Q
In this genetic disease, red blood cells cannot bind oxygen efficiently; the red blood cells also assume a characteristic sickle shape
A
Sickle-cell anemia
14
Q
Secondary structure of Proteins:
Within each amino acid residue are two bonds with reasonably free rotation:
A
(1) the bond between the a-carbon and the amino nitrogen of that residue and
(2) the bond between the a-carbon and the carboxyl carbon of that residue.
15
Q
Imagine a necklace made of playing cards:
Cards as Peptide Groups: Each playing card represents a peptide group in the chain. Just like cards are flat and rigid, peptide groups are planar (flat) structures.
Swivels as Bonds: The corners of these cards are connected by swivels (like tiny hinges). These swivels represent the bonds between the peptide groups. Unlike the rigid cards, these swivels allow the cards to rotate freely, giving the chain flexibility.
So, the peptide chain is like a flexible necklace made of rigid cards, where the cards are fixed in shape, but the links between them can swivel, allowing the chain to bend and twist.
A
16
Q
The side chains also play a vital role in determining the three-dimensional shape of a protein, but only the backbone is considered in the secondary structure.
A
17
Q
angles phi and psi are usually called what?
A
Ramachandran angles
18
Q
are used to designate rotations around the C-N and C-C bonds, respectively.
A
Ramachandran angles
19
Q
The conformation of a protein backbone can be described by specifying the values of phi and psi for each residue (-180° to 180°).
A
20
Q
one of the most frequently encountered folding patterns in the protein backbone
rodlike and involves the only one polypeptide chain
the coil of the helix is clockwise (right-handed)
A
alpha-helix
21
Q
one of the most important types of secondary structure, in which the protein backbone is almost fully extended
with hydrogen bonding between adjacent strands.
can give a two-dimensional array and can involve one or more polypeptide chains
A
beta-pleated sheet (beta-sheet)
22
Q
polypeptide chains lie adjacent to one another (parallel/anti-parallel)
R-groups alternate (first above then, below)
s-trans and planar
C=O and N-H groups of each peptide bond are perpendicular to the axis of the sheet
C=O—-H-N hydrogen bonds are between adjacent sheets and perpendicular to the direction of the sheet
A
beta-pleated sheet (beta-sheet)
23
Q
Alpha-helix
Counting from the N-terminal end, the C-O group of each amino acid residue is hydrogen bonded to the N-H group of the amino acid four residues away from it in the covalently bonded sequence.
C=O—-H-N hydrogen bonds are parallel to the helical axis
A
24
Q
The helical conformation allows a linear arrangement of
the atoms involved in the hydrogen bonds, which gives the bonds maximum strength and thus makes the helical conformation very stable
A
25
Alpha-helix: more infos
There are 3.6 residues for each turn of the helix, and the pitch of the helix (the linear distance between corresponding points on successive turns) is 5.4 Å
all R groups point outward from the helix
the s-trans and planar characteristics of each peptide bond in an alpha-helix contribute to the stability and rigidity of the helical structure, which is common and important type of secondary structure in proteins
26
is convenient for interatomic distances in molecules
Angstrom unit
1 Å = 10^-8
cm = 10^-10 m
27
Nanometers (1 nm = 10^-9 m)
Picometers (1 pm = 10^-12 m)
28
In SI units, the pitch of the a-helix is 0.54 nm or 540 pm.
29
Several factors can disrupt the a-helix. The amino acid
proline creates a bend in the backbone because of its cyclic structure. It cannot fit into the a-helix because
(1) rotation around the bond between the nitrogen and the a-carbon is severely restricted
(2) proline's a-amino group cannot participate in intrachain hydrogen bonding.
30
Other localized factors involving
the side chains include?
strong electrostatic repulsion owing to the proximity of several charged groups of the same sign (Lys and Arg or Glu and Asp)
crowding (steric repulsion) caused by the proximity if several bulky side chains (Val, Ile, Thr)
31
In the a-helical conformation, all the side chains lie outside the helix; there is not enough room for them in the interior
32
The peptide backbone in the b-sheet is almost completely extended. Hydrogen bonds can be formed between different parts of a single chain that is doubled back on itself (intrachain bonds) or between different chains (interchain bonds).
33
If the peptide chains run in the same direction (i.e., if they are all aligned in terms of their N-terminal and C-terminal ends),
a parallel pleated sheet is formed.
When alternating chains run in opposite directions, an antiparallel pleated sheet is formed
34
What is the reason for the name "pleated sheet?"
The hydrogen bonding between peptide chains in the b-pleated sheet gives rise to a repeated zigzag structure.
Note that the hydrogen bonds are perpendicular to the direction of the protein chain, not parallel to it as in the a-helix.
35
has three residues per turn and 10 atoms in the ring formed by making the hydrogen bond
310 (10 is a subscript)
36
Other common helices are designated 27 and 4.416, following the same nomenclature as the 310 helix.
37
a common nonrepetitive irregularity found in antiparallel beta-sheets
occurs between two normal beta-structure hydrogen bonds and involves two residues on one strand and one on the other,
beta-bulge
38
Protein folding requires that the peptide backbones and the secondary structures be able to change directions. Often reverse turn marks a transition between a secondary structure and another.
39
For steric (spatial) reasons, glycine is frequently encountered in reverse turns, at which the polypeptide
chain changes direction; the single hydrogen of the side chain prevents crowding
40
parts of proteins where the polypeptide chain folds back on itself
Reverse turns
41
two parallel strands of beta-sheets are connected by a stretch of alpha-helix
beta-alpha-beta subunit
42
consists of two antiparallel alpha helices
alpha-alpha subunit
43
In a b-meander, an antiparallel sheet is formed by a series of tight reverse turns connecting stretches of the polypeptide chain.
44
antiparallel sheet is formed when the polypeptide chain doubles back on itself in a pattern
a repetitive supersecondary structure formed when an antiparallel sheet doubles back on itself
Greek key
45
a repetitive supersecondary structure
do not allow us to predict anything about the biological function of the protein because they are found in proteins and enzymes with very dissimilar functions.
Motif
46
Protein sequences that allow for a b-meander or Greek key can often be found arranged into a b-barrel in the tertiary structure of the protein
47
Proteins with similar functions often have similar sequences, leading to specific domains (regions) that help with their function. There are different types of domains, including those that allow proteins to bind to DNA. Additionally, short sequences within a protein guide how it's modified after being made and where it goes in the cell. For instance, some sequences help form glycoproteins (proteins with attached sugars), others direct the protein to a membrane or signal it to be secreted, and some mark the protein for phosphorylation (adding a phosphate group) by an enzyme.
48
component of bone and connective tissue; the most abundant protein in vertebrates
organized in water-insoluble fibers of great strength
both intramolecularly and intermolecularly linked by covalent bonds formed by reactions of lysine and histidine residues.
Collagen
49
consists of three polypeptide chains wrapped around each other in a ropelike twist, or triple helix
Collagen fiber
50
Each of the three chains has, within limits, a repeating sequence of three amino acid residues, X-Pro-Gly or X-Hyp-Gly, where Hyp stands for hydroxyproline, and any amino acid can occupy the first position, designated by X.
51
Proline and hydroxyproline can constitute up to 30% of the residues in collagen.
52
is formed from proline by a specific hydroxylating enzyme after the amino acids are linked together
Hydroxyproline
53
In the amino acid sequence of collagen, every third position must be occupied by glycine. The triple helix is arranged so that every third residue on each chain is inside the helix. Only glycine is small enough to fit into the space available.
54
The three individual collagen chains are themselves helices that differ from the a-helix. They are twisted around each other in a superhelical arrangement to form a stiff rod. This triple helical molecule is called?
Tropocollagen
55
Symptoms of scurvy, such as bleeding gums and skin discoloration, are the results of fragile collagen. The enzyme that hydroxylates proline and thus maintains the normal state of collagen requires ascorbic acid (vitamin C) to remain active. Scurvy is ultimately caused by a dietary deficiency of vitamin C.
56
proteins whose overall shape is that of a long narrow rod
consist of long fibers or large sheets; mechanically strong
insoluble in water and dilute salt solutions
Fibrous proteins
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protein whose overall shape is more or less spherical
are water-soluble and have compact structures; their tertiary and secondary structures can be quite complex
soluble in water and salt solutions
most of their polar side chains are on the outside and interact with the aq. environment by hydrogen bonding and ion-dipole interactions
most nonpolar side chains are buried inside
nearly all have substantial sections of alpha-helix and beta-sheet
Globular proteins
58
The tertiary structure of a protein is its three-dimensional shape, which includes how all the atoms, side chains, and any attached groups are arranged. For fibrous proteins (long, rod-shaped), the secondary structure (like helices) largely determines the overall shape, with only the side chains' positions needing extra consideration.
In contrast, globular proteins (compact and spherical) require more information to understand their shape. Here, you need to know how the helices and sheets fold back on each other, as well as the positions of side chains and any attached groups. The interactions between side chains are crucial, as they often bring together parts of the protein that are far apart in the sequence but close in the final folded structure.
59
The primary structure of a protein, which is the sequence of amino acids, is determined by covalent peptide bonds. The higher levels of structure, such as the folding of the backbone (secondary structure) and the overall 3D shape (tertiary structure), rely on noncovalent interactions. If a protein has multiple subunits, their interactions (quaternary structure) also depend on noncovalent forces. These noncovalent interactions help the protein achieve its most stable, low-energy structure.
60
a major determinant of secondary structure; hydrogen bonds between the side chains of amino acids are also possible in proteins
Backbone hydrogen bonding
61
tend to cluster together in the interior of protein molecules as a result of hydrophobic interactions
Nonpolar residues
62
Electrostatic attraction between oppositely charged groups, which frequently occurs on the surface of the molecule, results in such groups being close to one another.
63
form covalent links between the side chains of cysteines
| read this in the ebook
64
Information about the locations of disulfide links can then be combined with knowledge of the primary structure to give the complete covalent structure of the protein.
65
The primary structure is the order of amino acids, whereas
the complete covalent structure also specifies the positions of the disulfide bonds.
66
Myoglobin and hemoglobin, which are oxygen-storage and transport proteins, don't have disulfide bridges but do have iron (Fe(II)) ions in a prosthetic group. On the other hand, enzymes like trypsin and chymotrypsin don't have metal ions but do have disulfide bridges. Most proteins rely on hydrogen bonds, electrostatic interactions, and hydrophobic interactions to stabilize their structure. A protein's three-dimensional shape results from the combined effect of all these stabilizing forces. Proline, an amino acid, can disrupt an alpha-helix and cause the chain to turn, but it's not the only amino acid that can cause turns or bends in a protein. These bends and non-helical or non-pleated regions are often called "random coils," though they are still stabilized by various forces that determine the protein's overall shape.
67
experimental technique used to determine the tertiary structure of a protein
X-ray crystallography
68
When a suitably pure crystal is exposed to a beam of X-rays, a diffraction pattern is produced on a photographic plate or a radiation counter.
69
The information is extracted from the diffraction patterns through a mathematical analysis known as a?
Fourier series
70
a method for determining the three-dimensional shape of proteins
depends on the distances between hydrogen atoms, giving results independent of those obtained in X-ray crystallography
Nuclear Magnetic Resonance (NMR)
71
large collections of data points are subjected to
computer analysis
uses a Fourier series to analyze results
2D NMR
72
It is similar to X-ray diffraction in other ways: It is a long process, and it requires considerable amounts of computing power and milligram quantities of protein
| read on this in the ebook
73
One way in which 2-D NMR differs from X-ray diffraction is that it uses protein samples in aqueous solutions rather than crystals.
74
was the 1st protein for which the complete tertiary structure was determined by the X-ray crystallography.
has a compact structure with the interior atoms very close to each other.
Myoglobin
75
an iron-containing cyclic compound found in the cytochromes, hemoglobin, and myoglobin
Heme
76
Myoglobin is a protein with eight alpha-helical regions and no beta-pleated sheets, with about 75% of its amino acids in these helices. The helices are stabilized by hydrogen bonds in the backbone and involve interactions with side chains. Polar residues are on the outside, while the interior is mostly nonpolar, except for two polar histidine residues that interact with the heme group and bound oxygen, crucial for myoglobin's function. The heme group, containing an Fe(II) ion and a porphyrin ring, fits into a hydrophobic pocket within the protein, significantly influencing the protein's conformation. Without the heme group, the protein (apoprotein) is less tightly folded.
77
The heme group is made up of an Fe(II) ion and protoporphyrin IX, which has four pyrrole rings linked by methione groups, forming a square planar structure. The Fe(II) ion has six coordination sites: four are occupied by nitrogen atoms from the pyrrole rings, one by a nitrogen atom from the imidazole side chain of a histidine residue (F8), and the sixth site binds oxygen. Another histidine residue (E7) near the heme acts as a gate, controlling oxygen's entry and ensuring proper binding to the heme.
78
Why does oxygen have imperfect binding to the heme group?
At first, it seems strange that oxygen doesn't bind perfectly to the heme group since the job of myoglobin and hemoglobin is to carry oxygen. However, the heme group can also bind to carbon monoxide (CO), which has a much stronger affinity than oxygen. The histidine residue (His E7) in myoglobin forces CO to bind at an angle, reducing its advantage over oxygen. This helps prevent CO from occupying all the oxygen-binding sites, which would be dangerous. Despite this, CO can still be toxic in larger amounts. Additionally, while hemoglobin and myoglobin need to bind oxygen, they must also release it, so binding too strongly would be problematic. Finally, the heme group must stay in its reduced form (Fe(II)) to bind oxygen; without the protein, the iron could oxidize to Fe(III), which won't bind oxygen.
79
the unravelling of the three-dimensional structure of a macromolecule caused by the breakdown of noncovalent interactions
Denaturation
80
This process of denaturation and refolding is a dramatic demonstration of the relationship between the primary structure of the protein and the forces that determine the tertiary structure.
Denaturation and reduction of disulfide bonds are frequently combined when complete disruption of the tertiary structure of proteins is desired. Under proper experimental conditions, the disrupted structure can then be completely recovered.
81
An increase in temperature favors vibrations within the molecule, and the energy of these vibrations can become great enough to disrupt the tertiary structure.
At either high or low extremes of pH, at least some of the charges on the protein are missing, and so the electrostatic interactions that would normally stabilize the native, active form of the protein are drastically reduced. This leads to denaturation.
82
The binding of detergents, such as sodium dodecyl sulfate (SDS), also denatures proteins.
detergents = disrupt hydrophobic interactions
83
Other reagents, such as urea and guanidine hydrochloride, form hydrogen bonds with the protein that are stronger than those within the protein itself. These two reagents can also disrupt hydrophobic interactions in much the same way as detergents
84
b-Mercaptoethanol is commonly used to break disulfide bridges in proteins, reducing them to sulfhydryl groups. Urea is added to help unfold the protein, making the disulfides more accessible to the reducing agent. If the conditions are right, the protein's original structure can be restored after both b-mercaptoethanol and urea are removed. These experiments support the idea that the amino acid sequence alone contains all the information needed to form a protein's complete three-dimensional structure.
85
the final level of protein structure and pertains to proteins that consist of more than one polypeptide chain; each chain is called a subunit
Quaternary structure
86
molecules consisting of two subunits
Dimers
87
molecules consisting of three subunits
Trimers
88
molecules consisting of four subunits
Tetramers
89
an aggregate of several smaller units (monomers); bonding may be covalent or noncovalent
Oligomer
90
the property of multisubunit proteins such that a conformational change in one subunit induces a change in another subunit
Allosteric
91
a tetramer, consisting of four polypeptide chains, two alpha-chains and two beta-chains
Hemoglobin
92
a cooperative effect whereby binding of the first ligand to an enzyme or protein causes the affinity for the next ligand to be higher
Positive cooperativity
93
The oxygen-binding curve of myoglobin is thus said to be hyperbolic.
In contrast, the shape of the oxygen-binding curve for hemoglobin is sigmoidal
94
a characteristic of a curve on a graph such that it rises quickly and the levels off
Hyperbolic
95
referring to an S-shaped curve on a graph, characteristic of cooperative interactions
Sigmoidal
96
This shape indicates that the binding of the first oxygen molecule facilitates the binding of the second oxygen, which facilitates the binding of the third, which in turn facilitates the binding of the fourth. This is precisely what is meant by the term?
Cooperative binding
97
Myoglobin has the function of oxygen storage in muscle. It must bind strongly to oxygen at very low pressures, and it is 50% saturated at 1 torr partial pressure of oxygen.
98
a unit of measure equal to that exerted by a column of mercury 1 mm high at zero degrees Celsius
Torr
99
The function of hemoglobin is oxygen transport, and it must be able both to bind strongly to oxygen and to release oxygen easily, depending on conditions.
100
In the alveoli of the lungs, where oxygen is picked up by hemoglobin, the oxygen pressure is 100 torr, leading to 100% saturation of hemoglobin. In the capillaries of active muscles, where oxygen is needed, the oxygen pressure drops to 20 torr, resulting in less than 50% saturation. This means hemoglobin readily releases oxygen in areas where it is most needed, like active muscles.
101
describes red blood cells' ability to adapt to changes in the biochemical environment, maximizing hemoglobin-oxygen binding capacity in the lungs while simultaneously optimizing oxygen delivery to tissues with the greatest demand.
Bohr's effect
102
Bohr Effect simplified:
High H⁺ (Low pH): When there's more acid (more H⁺ ions) in the blood, hemoglobin's structure changes slightly. This makes it less eager to hold onto oxygen. The H⁺ ions can attach to certain parts of hemoglobin, causing it to favor a shape that doesn't bind oxygen as well. This is especially important in areas where tissues are working hard and producing more acid, signaling that they need more oxygen.
Key Players: Specific parts of hemoglobin, like the beginning of its α-chains and a particular histidine (His146) on the β-chains, can grab onto these H⁺ ions. When His146 grabs a H⁺, it forms a connection with another part of the protein (Asp94), stabilizing hemoglobin in a form that releases oxygen.
Oxygen and Acid Balance: When hemoglobin is carrying oxygen, it's actually a little more acidic (has a lower pKa). When it lets go of the oxygen, it can grab onto more H⁺ ions, helping to balance the acid in your blood. This property helps hemoglobin manage both oxygen delivery and blood pH balance, depending on what the body needs.
103
Summary of the Bohr Effect;
Lungs = Activating Metabolizing Muscle
Higher pH than actively metabolizing tissue
Hemoglobin binds O2
Hemoglobin releases H+
Lower pH due to the production of H+
Hemoglobin releases O2
Hemoglobin binds H+
104
the application of computer methods to processing large amounts of information in biochemistry
Bioinformatics
105
similarity of monomer sequences in polymers
Homology
106
To predict the structure of a protein, the first step involves searching databases for known protein structures with similar sequences (homology). If the protein in question shares more than 25%-30% sequence similarity with a known protein, comparative modeling can be used to predict its structure based on the known protein's architecture. If the sequence similarity is lower, other methods like fold recognition, which compares the protein's sequence to known folding patterns, or de novo prediction, which uses fundamental principles of chemistry, biology, and physics, may be employed. These predictions can be validated by techniques like X-ray crystallography.
107
spherical aggregates of lipids arranged so that the polar head groups are in contact with water and the nonpolar tails are sequestered from water
Liposomes
108
Hydrophobic interactions are spontaneous processes. The entropy of the Universe increases when hydrophobic interactions occur.
Delta Suniv > 0
109
Importance of correct folding: simplified
Think of proteins as a long string of beads. Each bead represents a part of the protein, and the way these beads are arranged is called the primary structure. This arrangement contains all the instructions needed to fold the string into a specific shape, like a unique knot.
Now, just like a knot, this shape is crucial. It determines how the protein functions. In a perfect world, the string would always fold itself perfectly into the right knot. However, inside a cell, which is crowded and busy, the string might start to tangle up incorrectly or stick to other strings before it finishes folding.
If a protein folds correctly, it usually dissolves nicely in the cell or attaches where it’s needed. But if it folds incorrectly, those sticky parts that should be hidden inside stay exposed and cause the proteins to clump together. These clumps can be really harmful, leading to diseases like Alzheimer’s, Parkinson’s, and Huntington’s, where the brain is affected by these protein clusters.
So, the correct folding of proteins is like making sure each string becomes the right knot—essential for keeping everything in the cell working smoothly.
110
Protein-folding chaperones: simplified
Imagine proteins as strings that need to fold into a very specific shape to do their job. However, sometimes they need help to fold correctly, especially in the crowded environment of a cell. That's where chaperones come in.
Think of a chaperone as a guide or supervisor. Just like how in the old days, a chaperone might accompany young people on a date to ensure everything goes smoothly, protein chaperones help proteins fold correctly. They make sure that proteins don't get tangled up with the wrong partners or fold in a way that could lead to problems.
One of the first chaperones discovered is a family of proteins called hsp70. These proteins are produced by bacteria like E. coli when they're under stress, like when the temperature gets too high. Chaperones are found in all living organisms, from bacteria to humans, and they play a crucial role in making sure proteins function correctly.
A specific example is the chaperone for hemoglobin, a protein in our blood that carries oxygen. Hemoglobin is made of two types of chains: alpha (α) and beta (β). The body produces more α-chains than β-chains, and if too many α-chains are left on their own, they can clump together and cause problems. The chaperone called α-hemoglobin stabilizing protein (AHSP) prevents these α-chains from clumping and helps them pair with the β-chains to form functional hemoglobin.
111
What are the levels of protein structure?
Primary, secondary, tertiary, and quaternary.
Not all proteins have all four levels. For example, only proteins with multiple polypeptide chains have quaternary structure.
112
Why is it important to know the primary structure?
Primary structure is the order in which the amino acids are covalently linked. The primary structure of a protein can be determined by chemical methods. The amino acid sequence (the primary structure) of a protein determines its three-dimensional structure, which in turn determines its properties.
113
Why is the a-helix so prevalent?
practice this
The a-helix is stabilized by hydrogen bonds parallel to the helix axis within the backbone of a single polypeptide chain. The helical conformation allows a linear arrangement of the atoms involved in the hydrogen bonds, which gives the bonds maximum strength and thus makes the helical conformation very stable.
114
How is the b-sheet different from the a-helix?
The arrangement of atoms in the b-pleated sheet conformation differs markedly from that in the a-helix. The peptide backbone in the b-sheet is almost completely extended. Hydrogen bonds can be formed between different parts of a single chain that is doubled back on itself (intrachain bonds) or between different chains (interchain bonds). The hydrogen bonding between peptide chains in the b-pleated sheet gives rise to a repeated zigzag structure. The hydrogen bonds are perpendicular to the direction of the protein chain, not parallel to it as in the a-helix
115
Primary structure: sequence of amino acids
Secondary structure: localized conformation of the polypeptide backbone; alpha-helix and beta-pleated sheet
Tertiary structure: complete folding (1 individual subunit)
Quaternary structure: multiple subunits
116
frequently encountered in reverse turns for steric or spatial reasons, at which the polypeptide chain changes direction; the single hydrogen of the side chain prevent crowding
Glycine
117
because its cyclic structure has the correct geometry for a reverse turn, this amino acid is also frequently encountered in such turns
Proline
118
an anti-parallel sheet formed by a series of tight reverse turns connecting stretches of a polypeptide chain
beta-meander
119
created when beta-sheets are extensive enough to fold back on themselves
beta-barrel
120
Noncovalent hydrogen bonding (Polar, uncharged amino acids)
commonly involved in hydrogen bonding because they have side chains that can both donate and accept hydrogen bonds
Serine (Ser, S)
Threonine (Thr, T)
Asparagine (Asn, N)
Glutamine (Glu, Q)
Tyrosine (Tyr, Y) - can also participate in hydrophobic interactions due to its aromatic ring
Cysteine (Cys, C) - can form hydrogen bonds through its sulfur group
121
Hydrophobic interactions (Nonpolar, hydrophobic amino acids)
interact through hydrophobic interactions, which are driven by the tendency of nonpolar groups to avoid water and cluster together
Alanine (Ala, A)
Valine (Valine, V)
Leucine (Leu, L)
Isoleucine (Ise, I)
Methionine (Met, M)
Phenylalanine (Phe, F)
Tryptophan (Trp, W)
Proline (Pro, P) - less typical but contributes to hydrophobicity
122
Electrostatic (Ionic) interactions (Charged amino acids)
interactions, also known as ionic bonds, through attraction between opposite charges:
Positively charged (basic) amino acids:
Lysine (Lys, K)
Arginine (Arg, R)
Histidine (His, H)
Negatively charged (acidic) amino acids:
Aspartate (Asp, D)
Glutamate (Glu, E)
123
Covalent interactions (disulfide bridge)
Cysteine (Cys, C) - is the primary amino acid involved in covalent interactions through the formation of disulfide bonds; occurs when two cysteine residues form a covalent bond (disulfide bridge) between their sulfur atoms (-SH groups)
124
Several ways to denature proteins:
Heat
pH
Detergents
Urea
Guanadine hydrochloride
125
Myoglobin has a high affinity for oxygen; oxygen storage
Hemoglobin has a lower affinity for oxygen; oxygen transport; managing CO2 transport and maintaining the acid-base balance in the body
126
an allosteric effector because it binds to hemoglobin at a site other than the oxygen-binding site and alters hemoglobin's oxygen-binding properties, enhancing oxygen release where it is most needed
BPG (2,3-biphosphoglycerate)
127
Hsp70 - first chaperone proteins discovered
128
The alpha- and beta- globin genes are of different chromosomes. Excess alpha-chain is produced. If excess alpha-chains can interact, they form aggregates called alpha-inclusion bodies that damage red blood cells.
The globin chaperone (AHSP) binds to alpha-globin, keeping it from aggregating with itself and delivering it to the beta-globin so that the alpha-globin and the beta-globin can bind together to form the active tetramer
129
How can the three-dimensional structure of a protein be determined?
X-ray crystallography is used to determine the tertiary structure of a protein by growing perfect crystals under controlled conditions. When a pure crystal is exposed to X-rays, it produces a diffraction pattern on a photographic plate or radiation counter. This pattern arises from the scattering of X-rays by the electrons in the atoms. The scattered rays interfere constructively or destructively, creating a unique pattern for each type of molecule.
130
Why does oxygen have imperfect binding to the heme group?
Heme can bind to multiple molecules, including oxygen and carbon monoxide (CO). Free heme has a much higher affinity for CO than oxygen—about 25,000 times greater. However, in myoglobin, CO is forced to bind at an angle, reducing its advantage over oxygen by two orders of magnitude. This mechanism prevents CO, which is produced in small amounts during metabolism, from completely occupying the oxygen-binding sites on heme.
131
How does hemoglobin work?
Hemoglobin's main function is oxygen transport, and it must both bind oxygen strongly and release it easily based on the body's needs. Its oxygen binding is cooperative, meaning each bound oxygen makes it easier for the next to bind, and this process is influenced by ligands like H⁺, CO₂, and BPG. In contrast, myoglobin binds oxygen without cooperativity.
132
Can we predict the tertiary structure of a protein if we know its amino acid sequence?
It is possible, to some extent, to
predict the three-dimensional structure of a protein from
its amino acid sequence. Computer algorithms are based
on two approaches, one of which is based on comparison
of sequences with those of proteins whose folding pattern
is known. Another one is based on the folding motifs that
occur in many proteins.
133
What makes hydrophobic interactions favorable?
Hydrophobic interactions are spontaneous and increase the entropy of the universe. These interactions arise because water molecules surrounding nonpolar solutes are in an unfavorable, low-entropy state. When nonpolar molecules come together, it releases some of the water molecules, increasing the system's entropy. This process plays a key role in protein folding, where nonpolar regions of the protein tend to cluster together, driving the folding process.
