Protein Structure and Fonction Flashcards
1
Q
What do Proteins do?
A
They are involved in movement, catalysis, communication and transport
2
Q
How do proteins do all of their tasks
A
The essence of a protein’s function is in its interaction with other molecules
3
Q
What force stabilizes the shape of the protein
A
Non-covalent interactions
4
Q
What is a Zwitterion
A
A neutral (overall) ion with a positive and negative charges. It occurs when the pH is between ~2-9.5
5
Q
What is pKa?
A
Reflection of the strength of an acid
6
Q
What happens when we are at a pH > pKa
A
Then the [A-] > [HA]
7
Q
What happens when we are at a pH < pKa
A
Then the [A-] < [HA]
8
Q
What happens to the charge of the amino acids when the pH is at 1?
A
Overall positive
9
Q
What happens to the charge of the amino aids when the pH is at 11
A
Overall negative
10
Q
Are amino acids chiral molecules
A
Amino acids are chiral molecules
11
Q
What is a chiral molecule
A
A chiral molecule cannot be superimposed on its mirror image. The property of being asymmetric
12
Q
What are amino acids
A
20 incorporated into proteins. Classified by overall chemical properties of their side chains. They are nonpolar (hydrophobic), polar (uncharged), or charged (very polar).
13
Q
What are the particularities of nonpolar amino acid side chains
A
Lack reactive functional groups. Have mainly hydrocarbon side chains
14
Q
What are the nonpolar amino acid side chains
A
Alanine, Valine, Phenylalanine, Tryptophan, Leucine, Isoleucine, Methionine and Proline
15
Q
What is the side chain of Alanine
A
CH3
16
Q
What is the description of Alanine
A
Aliphatic R group (Methyl; Carbons and Hydrogens are not aromatic). Hydrophobic R group. Participates in hydrophobic interactions. Smallest chiral amino acid
17
Q
What is the side chain of Valine
A
CH3-CH-CH3
18
Q
What is the three letter format of Alanine
A
Ala
19
Q
What is the three letter format of Valine
A
Val
20
Q
What is the description of Valine
A
Aliphatic R group; Branched Carbon in the side chain. Highly hydrophobic R group.
21
Q
What the side chain of Leucine
A
CH2-CH-CH3
-CH3
22
Q
What is the three letter format of Leucine
A
Leu
23
Q
What is the description of Leucine
A
Aliphatic R group; Branched. Highly hydrophobic R group. Participates in hydrophobic interactions
24
Q
What is the side chain of Isoleucine
A
-H
C-CH2-CH3
-CH3
25
What is the the three letter format of Isoleucine
Ile
26
What is the description of Isoleucine
Aliphatic R group. Highly hydrophobic R group. Participates in hydrophobic interactions
27
What is the side chain of Phenylalanine
CH2-Benzene ring
28
What is the three letter format of Phenylalanine
Phe
29
What is the description of Phenylalanine
Aromatic R group. Highly hydrophobic R group. It is the highest hydrophobic R group of all amino acids. Participates in hydrophobic interactions
30
What is the side chain of Tryptophan
CH2 - NH pentene ring - benzene ring
31
What is the three letter formation of Tryptophan
Trp
32
What is the description of Tryptophan
Aromatic R group -heterocyclic. Mostly hydrophobic because it is bulky. Participates in hydrophobic interactions. Forms hydrogen bonds as a donor.
33
What is the side chain of Methionine
CH2-CH2-S-CH3
34
What is the three letter format of Methionine
Met
35
What is the description of Methionine
Aliphatic R group (it could be deemed honorary). Hydrophobic. Participates in hydrophobic interactions. Sulfur containing side group (thioether)
36
What is the side chain of proline
-CH2-CH2-CH2-
37
What is the three letter format of Proline
Pro
38
What is the description of Proline
Aliphatic side chain with distinctive cyclic structure. Secondary amino group. Hydrophobic but often found on protein surface because it has unique structural characteristics.
39
What are the particularities of polar amino acid side chains
Polar. Reactive due to presence of functional groups. Polar amino acids have side chains that contain an electronegative atom. Not all R groups have ionizable R group
40
What are the polar amino acids
Serine, Threonine, Tyrosine, Cysteine, Asparagine, Glutamine, Histidine and Glycine
41
What is the side chain of Glycine
H
42
What is the three letter format of Glycine
Gly
43
What is a description of Glycine
Achiral. Weakly polar. Small so it is flexible.
44
What is the side chain of Serine
CH2-OH
45
What is the three letter format of Serine
Ser
46
What is the description of Serine
Polar, uncharged. Contains hydroxyl group. Forms hydrogen bonds as an acceptor and donor; but it is typically a donor. Can be modified through phosphorylation
47
What is the side chain of Threonine
-OH
C-CH3
-H
48
What is the three letter format of Threonine
Thr
49
What is a description of Threonine
Polar, uncharged. Contains a hydroxyl. group, forms hydrogen bonds as an acceptor and donor but it is typically a donor. Can be phosphorylated
50
What is the side chain of Tyrosine
CH2-Benzene ring-OH
51
What is the three letter format of Tyrosine
Tyr
52
What is the pKa of Tyrosine
10.5
53
What is the description of Tyrosine
Weakly polar, uncharged. Aromatic R group, phenol and can participate in hydrophobic interactions. Contains hydroxyl group. Forms hydrogen bonds as an acceptor and donor; typically it is a donor
54
What is the side chain of Cysteine
CH2-SH
55
What is the three letter format of Cysteine
Cys
56
What is the pKa of Cysteine
8.5
57
What is the description of Cysteine
Polar, uncharged. Sulfur-containing side chain (thiol group - SH). Can form hydrogen bonds as a donor. Can form a thiolate anion (S-). Forms disulfide bonds with another Cysteine
58
How does Cystine form
Thiols in neighbouring cysteine resides can undergo oxidation to form a disulfide bond
59
What is Cystine
-NH3(+)(on the last CH)
(-)OOC-CH-CH2-S-S-CH2-CH-COO(-)
-NH3(+) (on the first CH)
60
What is the side chain of Asparagine
=O
CH2-C
-H2N
61
What is the three letter format of Asparagine
Asn
62
What is the description of Asparagine
Amide-containing side chain. Carboxamide functional group. Polar, uncharged. Forms hydrogen bonds as donor and acceptor. Nitrogen acts as donor and Oxygen acts as acceptor
63
What is the side chain of Glutamine
=O
CH2-CH2-C
-H2N
64
What is the three letter format of Glutamine
Gln
65
What is the description of Glutamine
Amide-containing side chain. Carboxamide functional group. Polar, uncharged. Forms hydrogen bonds. Nitrogen acts a donor and Oxygen acts as an acceptor
66
What is the side chain of Histidine
CH2-Heterocyclic (N and HN) pentene ring
67
What is the three letter format of Histidine
His
68
What is the pKa of Histidine
6.0. Side chain can be acidic or basic at neutral pH. Base form is predominant when pH is at or above 7.0. Acid form is predominant when pH is below 6.0
69
What is the description of Histidine
Polar, charged/uncharged. Histidine resides important in many enzyme catalyzed reactions. Proton donor (acid) / acceptor (base). Hydrogen bonding capability - proton donor or acceptor
70
What is the side chain of Aspartate
CH2-COO(-)
71
What is the three letter format of Aspartate
Asp
72
What is the pKa of Aspartate
4.0. Negatively charged R group at pH 7. Second carboxyl group. "Acidic" amino acid
73
What is the description of Aspartate
"Acidic" amino acid. Very polar. Forms hydrogen bonds, hydrogen bond acceptor. At pH 1 called aspartic acid.
74
Why does Aspartate change to Aspartic acid at pH 1
Contains a neutral functional group the COO(-) becomes COOH
75
What is the three letter format of Glutamate
Glu
76
What are the charged amino acids
Aspartate, Glutamate, Lysine, and Arginine
77
What are the negatively charged charged amino acids
Aspartate and Glutamate
78
What are the positively charged charged amino acids
Lysine and Arginine
79
What is the pKa of Glutamate
4.0. Negatively charged R group at pH 7. Second carboxyl group. "Acidic" amino acids.
80
What is the description of Glutamate
Very polar. Forms hydrogen bonds, Hydrogen bond acceptor. At pH 1 called glutamic acid
81
Why does Glutamate become Glutamic acid at pH 1
Contains a neutral functional group the COO(-) becomes COOH
82
What is the side chain of Lysine
CH2-CH2-CH2-CH2-NH3(+)
83
What is the three letter format of Lysine
Lys
84
What is the pKa of Lysine
10.0. Positively charged side group at pH 7. "Basic" amino acid
85
What is a description of Lysine
"Basic" amino acid. Side group contains an amino, so the total group contains 2 primary amino groups. Forms hydrogen bonds. It is a hydrogen bond donor and at pH 14 would be allow it to act as a hydrogen bond acceptor. Very polar
86
What is the side chain of Arginine
=NH2(+)
CH2-CH2-CH2-NH-C
-H2N
87
What is the three letter format of Arginine
Arg
88
What is the pKa of Arginine
12.5. Positively charged side group at pH 7. Guanido group. "Basic" amino acid. Never deprotonate under physiological conditions
89
What is a guanido group
Three nitrogen that are attached to a carbon
90
What is a description of Arginine
"Basic" amino acid. Never deprotonate under physiological conditions. Very polar. Forms hydrogen bonds as a donor and 5 are in the side chain.
91
What are the exceptions of the amino acids that don't use the first three letters of their names
Asparagine (Asn), Glutamine (Gln), Isoleucine (Ile), and Tryptophan (Trp)
92
Where are polar side chains found
They are on in proteins on the surface because it can interact with water. It includes polar uncharged and polar charged amino acids
93
Where are the non-polar side chains found
Non-polar side chains are usually found buried in the protein core. Minimizes interactions with water (hydrophobic effect)
94
How do name when many amino acids joined together
Two peptides: dipeptide
Three peptides: tripeptide
Four peptides: tetrapeptide
etc.
95
What is a peptide/oligopeptide
General term for a larger number of amino acids, often refers to synthetic peptides (<40 residues)
96
What is a polypeptide
Produced by a translational process. Long chain of amino acids usually produced naturally.
97
What is a protein
Large polypeptide (or >1 polypeptide) with a biological function
98
What is a dipeptide
When you have Ser.Ala it is not equivalent to Ala.Ser. Sense of direction is important in distinguishing different molecules/and ulitmately sequencing. Direction is Nitrogen to Carbon by convention
99
What is a tetrapeptide
Only the terminal amino and carboxylate groups in a peptide retain their charge. The others are eliminated by the formation of peptide bonds. Side chains retain their charge (if they have one)
100
What is the backbone of a tetrapeptide
All non-sidechain R group atoms (Nitrogen-Carbon-Carbon-etc.)
101
What is the primary structure of proteins
The sequence of amino acids in a polypeptide is the "primary structure." Covalent peptide bonds join each amino acid to the next. Every protein or polypeptide has a unique sequence
102
What are the characteristics of peptide bonds
They are rigid and planar
103
What are properties of peptide bonds
The electrons in peptide bonds are somewhat delocalized generating two resonance forms. Peptide bonds therefore exhibit double-bond character with no rotation around the C-N bond. The functional groups in peptide bonds are potential Hydrogen bond acceptors or donors
104
What happens because the peptide bonds are rigid and planar
The backbone of a polypeptide includes the Alpha carbon atoms and those involved in peptide bonds
105
What occurs in the folding conformations in proteins
Folding conformations are limited because two oxygens take the same space they minimize steric conflicts.
106
What are the hydrogen bonds in polypeptide backbones
The chemical groups found in peptide bonds are highly polar. Carbonyl groups are hydrogen bond acceptors. NH groups are hydrogen bond acceptors. They maximize their hydrogen bonding capabilities.
107
What are some secondary structures of proteins
Local folding of the polypeptide backbone. Allows for hydrogen bonding of the groups in the polypeptide backbone (C=O, N-H). "Regular" secondary structures occur when every amino acid in a segment of the polypeptide adopts the same geometry. A few regular patterns occur: alpha-helix and beta-sheet which both minimize steric conflicts and maximize hydrogen bonds
108
What occurs in an alpha-helix
The carbonyl oxygen of each residue forms a hydrogen bond with the backbone -NH group four resides downstream (C1...N5, C2...N6, etc). Complete hydrogen potential satisfied for backbone. Except for amino acid residues at either end all the backbone CO and NH groups are hydrogen bonded to one another in the helix. There is a right-handed twist.
109
What happens to the side chains in an alpha-helix
Helix is SOLID with atoms in the polypeptide backbone in Van der Waals contact with one another in the center. Amino acids project outwards residues 3-4 apart in the primary structure are close in the secondary structure
110
What are parallel and anti-parallel Beta-sheets
Multiple beta-strands are arranged side by side. Strands a joined by loops or other structures. Parallel strands appear to join diagonally and anti-parallel join vertically
111
How are beta-sheets drawn
They are often drawn as arrows. The arrows are shown pointing from the nitrogen-terminal to the carbon-terminal end.
112
How are anti-parallel sheets drawn
It flows from one arrow to other to form an easy zig-zag
113
How are parallel sheets drawn
The strands overlap because the arrows will be point the same direction.
114
Where are side chains located on a beta-sheet
Side chains are located above and below the plane of the sheet; they are alternating
115
What forces stabilize alpha-helices
Hydrogen bonds between the backbone CO and NH groups in the same helices
116
What forces stabilize beta-helices
Hydrogen bonds between CO and NH groups of neighbouring strands
117
What makes an irregular secondary structure
Distinct elements of regular secondary structure are linked together by polypeptide loops of various sizes ranging from simple hairpins to longer loops. These structures are irregular.
118
What is the tertiary structure of a protein
Arrangement of all atoms in a single polypeptide. Arrangement of secondary structure in relation to one another. Positions of amino acid side chains. Prosthetic groups (heme, FAD, etc.)
119
What are the two morphologies of tertiary protein structures
Fibrous (elongated) and Globular (compact)
120
What are fibrous proteins
Practically insoluble into aqueous solutions. Form long protein filaments - limited resides with repeats. Usually structural or connective proteins.
121
What are globular proteins
Practically soluble in aqueous solutions. Fold into compact structures with nonpolar cores and polar surfaces.
122
What structures do fibrous proteins adopt
Fibrous proteins (like collagen) tend to adopt linear extended structures
123
How variable is the structure of globular proteins
The tertiary structure in globular proteins is highly variable
124
Where are hydrophobic side chains found in a globular protein
Hydrophobic side chains are most likely to be found in the interior of a globular protein
125
Where are hydrophilic side chains found in a globular protein
Hydrophilic side chains are most likely to be found on the surface of a globular protein
126
Where are loops located in a globular protein
Loops tend to be located on the surface
127
Where are irregular structures located in a globular protein
Irregular structures are on the surface
128
Where are the regular structures located in a globular protein
Regular structures are in the core
129
What impacts the shape of the globular proteins
The shape of globular proteins depend of the relative positions of hydrophobic amino acids in the proteins primary structures
130
How does the hydrophobic effect have an impact on globular proteins
The hydrophobic effect is the "driving force" via which soluble globular proteins adopt and maintain their tertiary structure
131
What is Ion Pairs ("Salt Bridges")
Electrostatic interactions between closely positioned formal charged groups. Like hydrogen bonds, these helps to "fine tune" and stabilize secondary and tertiary structures
132
What are the positive charges in ion pairs
N-terminus, Lys, Arg and His
133
What are the negative charges in ion pairs
C-terminus, Asp, Glu, Tyr and Cys
134
What can impact the charges of ion pairs
Charges will depend on pH of the environment
135
What is Disulfide bonds/bridges
Covalent bonds between closely positioned cysteines. These form stabilizing crosslinks for extracellular proteins (or proteins in the lumen)
136
What happens in the cytosol of Disulfide bonds/bridges
In the cytosol, cysteines do not oxidize to cystine as it is a reducing environment
137
What are the two main parts of protein structure
Domain and Motif
138
What is the domain of protein structure
A polypeptide segment that has folded into a single structural unit with a hydrophobic core. Proteins may contain more than one domain
139
What is the motif of protein structure
A short region of polypeptide with a recognizable 3D shape. Zinc fingers. May be found in many contexts
140
What are some examples of protein domains
Pyruvate kinase and Cow gamma crystalline
141
How many protein domains are in pyruvate kinase
It is composed of a single polypeptide chain, which can be divided into 3 domains
142
How many protein domains are in cow gamma cystalline
Contains two domains one polypeptide
143
What are some motifs in protein structure
Helix-loop-helix, Coiled coil, Helix bundle, Beta-alpha-beta unit, hairpin, beta-meander, greek key and beta sandwich
144
What are zinc fingers
An example of a structural motif including a prosthetic group.
145
What are prosthetic groups
A non-peptide component that is permanently incorporated into a protein
146
What are some examples of prosthetic groups
Zinc fingers and functional groups such as heme in hemoglobin
147
How are globular proteins impacted by outside forces
Globular proteins are stabilized by weak noncovalent forces and easily unfolded or "denatured" by heat, changes in pH, salt and detergents.
148
What can disrupt Disulfide bonds
Reducing agents (DTT) can disrupt disulfide bridges
149
What are quaternary structures
Proteins composed of more than one polypeptide chain. Each polypeptide chain is called a subunit.
150
How are quaternary structures named
Named by number and types of subunits.
2 subunits: Dimer
3 subunits: Trimer
etc.
151
What is the name of identical subunits in quaternary structures
Homodimer
152
What is the name of non-identical subunits in quaternary structures
Heterodimer
153
How are quaternary structures stabilized
They are stabilized by hydrophobic interactions and hydrogen bonds, ion pairs "fine-tune)
154
How is the function of a protein determined
The function of a protein is determined absolutely by its structure.
155
What is the name of the subunit of Myoglobin
Monomer with no quaternary structure
156
What is the name of the subunit of Hemoglobin
Oligomer with a quaternary structure
157
What is the role of Hemoglobin
Hemoglobin red blood cells binds O2 in the lungs and releases it in the tissues
158
What is the role of Myoglobin
Myoglobin binds O2 in muscle cells. Facilitates O2 diffusion through muscle tissue. Acts as a local reserve of O2 during intense exercise. Stores O2 in aquatic animals.
159
What is the role for both Hemoglobin and Myoglobin
Both bind oxygen reversibly but bind it with different affinities and under different conditions
160
What is the structure of Myoglobin
Polar propionyl groups. Porphyrin ring held in place by hydrophobic interactions AND by coordination bond between Fe2+ and a histidine which is called the proximal histidine
161
What does the proximal histidine do
1. Binds heme into heme-binding pocket
| 2. Prevents oxidation of iron atom
162
What is the structure of heme
Heme is circular and planar. In heme, the porphyrin ring contains an Fe2+ ion coordinated between the four Nitrogen atoms. The two substituents at the bottom of the ring are polar (uncharged) propionyl groups whereas the rest are non-polar aliphatic groups
163
Where does Fe2+ ion position in Heme
5th coordination position
164
Where does O2 atom position in Heme
6th coordination position
165
What is the oxygen binding site in myoglobin
Binding sites are designed precisely to optimize binding specificity and affinity
166
How much stronger is the free Heme carbon monoxide affinity than O2
Free Heme Carbon monoxide affinity is ~2500 times higher than O2
167
How much stronger is Myoglobin / Hemoglobin carbon monoxide affinity than O2
Myoglobin / Hemoglobin carbon monoxide ~250 times higher than 02.
168
What are the two types of globin with within the tetramer of Hemoglobin
2 alpha subunits (alpha-globin) and 2 beta subunits (beta-globin)
169
What is the tertiary structure of beta-globin, alpha-globin and myoglobin
All 3 polypeptides comprise 8 alpha-helices with a heme binding pocket between helices E and F (plus irregular structures).
170
How much of the primary structure is approximately identical
20-25% identical
171
What are homologous proteins/polypeptides
They share an ancestral heritage
172
What is the composition of hemoglobin (Hb)
4 polypeptide chains, 2 alpha-globin chains, 2 beta-globin chains and 1 heme/polypeptide - binds 4 O2/Hb
173
What is the composition of Myoglobin
1 polypeptide chain, 1 heme - binds 1 O2/Mb
174
What are conservative substitutions
Relatively minor effects on structure/function. Examples are: Leu and Ile, and Thr and Ser
175
What are critical substitutions
Change structure and function depending on location. Examples are: polar to nonpolar, Ser and Val, and Phe and Lys
176
How does the alpha-subunit and beta-subunit of hemoglobin binds O2 in the same manner as myoglobin
Oxygen at the 6th coordination position of an Fe2+ ion in a heme ring
177
What are the critical resides that are invariant
Several critical residues in/near the oxygen binding are invariant (do not change) among the three polypeptides: -His F8, and - His E7
178
What does a hyperbolic curve indicate
Hyperbolic curve is indicative of constant affinity
179
What is an example of a hyperbolic curve
Myoglobin
180
What is a sigmoidal curve
A sigmoidal curve is diagnostic of cooperative binding affinity
181
What is an example of sigmoidal curve
Hemoglobin
182
What is the function of Myoglobin and Hemoglobin
Reversibly bind/release O2
183
What is the function of Myoglobin that is different than Hemoglobin
O2 transport within tissue
184
What is the function of Hemoglobin that is different than Myoglobin
O2 transport from lungs to tissues
185
What is the point of the sigmoidal binding curve
Cooperative process (positive cooperativity), necessary for efficient O2 delivery, and reflects change in binding affinity; change in tertiary structure and quaternary structure of hemoglobin
186
How does Hb change its affinity for O2?
Two Distinct Structures of Hemoglobin, T state or R state
187
What does T state look like
In the T state, in deoxyhemoglobin, a His residue on the beta subunit fits between a Thr and a Pro residue in the alpha-subunit
188
What does R state look like
In the R state, upon oxygenation, the hemoglobin changes shape and the His residue is now located between two Thr residues on the alpha subunit
189
What is the O2 affinity to T state
Low affinity for O2
190
What is the O2 affinity to R state
High affinity for O2
191
Does T state or R state have deoxy hemoglobin
T state
192
Does T state or R state have oxy hemoglobin
R state
193
What size is the central cavity of T state
Larger central cavity
194
What size is the central cavity of R state
Smaller central cavity
195
What does Allostery mean
"Other" "Space"
196
What are allosteric effectors
Compounds which, upon binding, alter affinity at other binding sites
197
What is Homoallosteric
Binding of the effector affects further binding of the same compounds
198
What is Heteroallosteric
Binding of the effect affects further binding of the different compound
199
What are activators in allostery
Increase binding affinity they are positive effectors
200
What are inhibitors in allostery
Decrease binding affinity they are negative effectors
201
What is the Action of Allosteric Effectors
Equilibrium between T and R is being affected by the binding of X. The binding of a ligand/substrate at one site on a macromolecule affects the affinity of other sites for the SAME ligand.
202
What are the conformational changes in oxygen binding to hemoglobin
The iron moves into plane of heme (when they are changing from T state to R state). The proximal histidine moves with the iron atoms
203
What are the events in O2 binding to Hemoglobin
T-state (no O2 bound). O2 binds to a subunit.. Fe2+ moves into plane of heme. Histidine F8 moves with iron. Helix F moves, Subunit interface changes. Subunit interface change affects other subunits. Helix F/His F8/Fe2+ movement. Oxygen binding site becomes high affinity (R). Oxygen binds more readily to other binding sites
204
What kind of allosteric effect does O2 have
O2 is a homoallosteric activator
205
What kind of allosteric effect does BPG have
BPG is a heteroallosteric inihibiter (for O2)
206
What is BPG
2,3-bisphophoglycerate
207
What kind of allosteric effect does H+ have
H+ is a heteroallosteric inhibitor (for 02)
208
What does BPG and H+ do in the T state
BPG and H+ stabilize T state they are both part of the 'Bohr effect'.
209
How is BPG essential to the T state of Hemoglobin
Small and highly negative. Negative Allosteric Effector of O2 binding
210
How does BPG bind to Deoxyhemoglobin
BPG binds in the central cavity of the deoxyhemoglobin (T state). The negative charges on the BPG interaction with positively charged groups on the protein that are directed into the central cavity. 4 His, 2 Lys, 2 N-terminal residues The central cavity in oxyhemoglobin (R state) is too small to accommodate BPG.
211
What is the result of metabolism generating protons
It lowers pH
Examples:
ATP + H2O → ADP + Pi + H (+)
CO2 + H2O → HCO3 (-) + H (+)
212
What does lowering pH lead do to side chains and functional groups
Lowering pH leads to protonation of side chains and functional groups
Examples:
His + H (+) → His (+)
NH2 + H (+) → NH3 (+)
213
What does the Bohr Effect do
pH dependence of O2 binding. As we lower the pH oxygen affinity decreases. As we raise the pH oxygen affinity increases
214
In the lungs and in the tissues how does Hemoglobin exist
In the lungs and in the tissues, any given molecule of Hb can exist in either the T state or the R state. The lungs have a high pp O2 and a relatively high pH. The R state is thus favoured, and when oxygen binds it triggers the switch to the R form. Actively respiring tissues have a relatively low pH and a low pp O2. The T state is favoured, and oxygen is released.
215
What affects the proportion of molecules
Their proportion of molecules that are in either form (the position of the equilibrium) depends on the presence of BPG, on the [H+] ions, and on the pp O2. The proportion of molecules that are in either form (high or low affinity) determines how much oxygen is bound or released.
216
How do sickled red blood cells come to be
B-chain Glu6 is replace with Val. (Polar charged amino acid change with to a nonpolar amino acid) Critical substitution
217
What are the effects of the sickle mutation
In Hb there is a small hydrophobic surface patch which is exposed between the E and F helices during the transition from R to T form. The hydrophobic Val binds here, causing the Hb molecules to aggregate into long polymers/fibres.
218
What is Fetal Hemoglobin
2 alpha and 2 gamma subunits. (Gamma subunit replaces the Beta subunit.) Gamma subunit is the adult beta subunit. (Homologous (73% identical to Beta subunit). Substitution of His143 with serine) His143 is one of the His residues that is involved in binding BPG. (Decreased BPG affinity. Increased O2 affinity)
219
What are the roles of HisF8 (proximal histidine)
Attachment of heme. Prevent oxidation of Fe2+
220
What is the roles of HisE7 (distal histidine)
Assist O2 binding. Decreases affinity of CO
221
What do the 4 Histidine in the central cavity and subunit interface do
4 His in the central cavity and the subunit interface are part of the “Bohr effect.”
