2.(a) The two diagrams on the right compare O2 binding pro- perties of Hb Kariya, a human hemo- globin characterized by the mutation Lys(a40)Glu, with those of HbA as a function of pH ranging from pH 9.0 to pH 6.95. One O2 saturation curve () illustrates the O2 binding proper- ties at pH 7.5 in the presence of 2 mM inositol hexaphosphate (IHP). (IHP is found in avian red blood cells. and binds more tightly than BPG be- cause of the additional negative charges.) log [Y/(1 - Y)] Hb Kariya + IHP (b) The diagram on the right illustrates sche- matically the interaction of the side chain of the aLys40 residue with the C-terminal -COOH group of the B-sub- unit in HbA. In Hb Kariya with a Lys(a40)Glu mutation, which allosteric conformation R or T is destabilized, and which allosteric HbA conformation is illustrated on the right? Explain log (P) Excluding the O2 saturation curve collected in the presence of inositol-hexaphosphate (IHP), indicate with an arrow for both hemoglobins the plot corresponding to pH 9 and that corresponding to pH 6.95.Explain the basis of your choice. 137 105 138 103 88 (c) Estimates of the dissociation equilibrium constants for the first O₂ to be bound and for the fourth O2 to be bound at pH 6.95 are compared in the table on the right for HbA and Hb Kariya. For the two different hemoglobins, the values for K₁ differ greatly while those for K4 are nearly equivalent. Also the values of K₁ and K4 for Hb Kariya are more similar to each other than are those for HbA. Explain the structural origin for these differences. 92 (1020 HbA B₂ FG corner 96 100) val (98 HbA Hb Kariya 95 93 97 0.. 144 94 + IHP (145 + 41 44 146 40 C helix 45 Dissociation Con- stant (mm Hg) K₁ K4 36 0.15 2.1 0.24 (d) In the two Hill plots in part (a) above, the addition of IHP has shifted the O2 affinity of HbA but there is no apparent change in the Hill coefficient or the degree of allostery. However, addition of IHP to the solution of Hb Kariya results in a clear increase in Hill coefficient, albeit small, in addition to decreased O2 binding affinity. What are the minimum requirements for allostery in a multi-subunit pro- tein and why are these satisfied in Hb Kariya in the presence of IHP?
2.(a) The two diagrams on the right compare O2 binding pro- perties of Hb Kariya, a human hemo- globin characterized by the mutation Lys(a40)Glu, with those of HbA as a function of pH ranging from pH 9.0 to pH 6.95. One O2 saturation curve () illustrates the O2 binding proper- ties at pH 7.5 in the presence of 2 mM inositol hexaphosphate (IHP). (IHP is found in avian red blood cells. and binds more tightly than BPG be- cause of the additional negative charges.) log [Y/(1 - Y)] Hb Kariya + IHP (b) The diagram on the right illustrates sche- matically the interaction of the side chain of the aLys40 residue with the C-terminal -COOH group of the B-sub- unit in HbA. In Hb Kariya with a Lys(a40)Glu mutation, which allosteric conformation R or T is destabilized, and which allosteric HbA conformation is illustrated on the right? Explain log (P) Excluding the O2 saturation curve collected in the presence of inositol-hexaphosphate (IHP), indicate with an arrow for both hemoglobins the plot corresponding to pH 9 and that corresponding to pH 6.95.Explain the basis of your choice. 137 105 138 103 88 (c) Estimates of the dissociation equilibrium constants for the first O₂ to be bound and for the fourth O2 to be bound at pH 6.95 are compared in the table on the right for HbA and Hb Kariya. For the two different hemoglobins, the values for K₁ differ greatly while those for K4 are nearly equivalent. Also the values of K₁ and K4 for Hb Kariya are more similar to each other than are those for HbA. Explain the structural origin for these differences. 92 (1020 HbA B₂ FG corner 96 100) val (98 HbA Hb Kariya 95 93 97 0.. 144 94 + IHP (145 + 41 44 146 40 C helix 45 Dissociation Con- stant (mm Hg) K₁ K4 36 0.15 2.1 0.24 (d) In the two Hill plots in part (a) above, the addition of IHP has shifted the O2 affinity of HbA but there is no apparent change in the Hill coefficient or the degree of allostery. However, addition of IHP to the solution of Hb Kariya results in a clear increase in Hill coefficient, albeit small, in addition to decreased O2 binding affinity. What are the minimum requirements for allostery in a multi-subunit pro- tein and why are these satisfied in Hb Kariya in the presence of IHP?
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
Problem 1P
Related questions
Question
![2.(a)
The two diagrams on
the right compare O2 binding pro-
perties of Hb Kariya, a human hemo-
globin characterized by the mutation
Lys(a40)Glu, with those of HbA as a
function of pH ranging from pH 9.0 to
pH 6.95. One O2 saturation curve
() illustrates the O2 binding proper-
ties at pH 7.5 in the presence of 2
mM inositol hexaphosphate (IHP).
(IHP is found in avian red blood cells.
and binds more tightly than BPG be-
cause of the additional negative
charges.)
log [Y/(1 - Y)]
Hb Kariya
+ IHP
(b)
The diagram on the right illustrates sche-
matically the interaction of the side chain of the aLys40
residue with the C-terminal -COOH group of the B-sub-
unit in HbA. In Hb Kariya with a Lys(a40)Glu mutation,
which allosteric conformation R or T is destabilized,
and which allosteric HbA conformation is illustrated on
the right? Explain
log (P)
Excluding the O2 saturation curve collected in the presence of inositol-hexaphosphate (IHP), indicate
with an arrow for both hemoglobins the plot corresponding to pH 9 and that corresponding to pH
6.95.Explain the basis of your choice.
137
105
138
103
88
(c)
Estimates of the dissociation equilibrium constants for
the first O₂ to be bound and for the fourth O2 to be bound at pH
6.95 are compared in the table on the right for HbA and Hb Kariya.
For the two different hemoglobins, the values for K₁ differ greatly
while those for K4 are nearly equivalent. Also the values of K₁ and
K4 for Hb Kariya are more similar to each other than are those for
HbA. Explain the structural origin for these differences.
92
(1020
HbA
B₂ FG corner
96
100)
val (98
HbA
Hb Kariya
95 93
97
0..
144
94
+ IHP
(145
+
41 44
146
40
C helix
45
Dissociation Con-
stant (mm Hg)
K₁
K4
36
0.15
2.1
0.24
(d)
In the two Hill plots in part (a) above, the addition of IHP has shifted the O2 affinity of HbA
but there is no apparent change in the Hill coefficient or the degree of allostery. However, addition of
IHP to the solution of Hb Kariya results in a clear increase in Hill coefficient, albeit small, in addition to
decreased O2 binding affinity. What are the minimum requirements for allostery in a multi-subunit pro-
tein and why are these satisfied in Hb Kariya in the presence of IHP?](/v2/_next/image?url=https%3A%2F%2Fcontent.bartleby.com%2Fqna-images%2Fquestion%2F7e3218aa-1b65-42a2-9071-7edb43c3a555%2F695b687d-7bd9-47e4-a195-fe39ffede40a%2F0omilq8_processed.png&w=3840&q=75)
Transcribed Image Text:2.(a)
The two diagrams on
the right compare O2 binding pro-
perties of Hb Kariya, a human hemo-
globin characterized by the mutation
Lys(a40)Glu, with those of HbA as a
function of pH ranging from pH 9.0 to
pH 6.95. One O2 saturation curve
() illustrates the O2 binding proper-
ties at pH 7.5 in the presence of 2
mM inositol hexaphosphate (IHP).
(IHP is found in avian red blood cells.
and binds more tightly than BPG be-
cause of the additional negative
charges.)
log [Y/(1 - Y)]
Hb Kariya
+ IHP
(b)
The diagram on the right illustrates sche-
matically the interaction of the side chain of the aLys40
residue with the C-terminal -COOH group of the B-sub-
unit in HbA. In Hb Kariya with a Lys(a40)Glu mutation,
which allosteric conformation R or T is destabilized,
and which allosteric HbA conformation is illustrated on
the right? Explain
log (P)
Excluding the O2 saturation curve collected in the presence of inositol-hexaphosphate (IHP), indicate
with an arrow for both hemoglobins the plot corresponding to pH 9 and that corresponding to pH
6.95.Explain the basis of your choice.
137
105
138
103
88
(c)
Estimates of the dissociation equilibrium constants for
the first O₂ to be bound and for the fourth O2 to be bound at pH
6.95 are compared in the table on the right for HbA and Hb Kariya.
For the two different hemoglobins, the values for K₁ differ greatly
while those for K4 are nearly equivalent. Also the values of K₁ and
K4 for Hb Kariya are more similar to each other than are those for
HbA. Explain the structural origin for these differences.
92
(1020
HbA
B₂ FG corner
96
100)
val (98
HbA
Hb Kariya
95 93
97
0..
144
94
+ IHP
(145
+
41 44
146
40
C helix
45
Dissociation Con-
stant (mm Hg)
K₁
K4
36
0.15
2.1
0.24
(d)
In the two Hill plots in part (a) above, the addition of IHP has shifted the O2 affinity of HbA
but there is no apparent change in the Hill coefficient or the degree of allostery. However, addition of
IHP to the solution of Hb Kariya results in a clear increase in Hill coefficient, albeit small, in addition to
decreased O2 binding affinity. What are the minimum requirements for allostery in a multi-subunit pro-
tein and why are these satisfied in Hb Kariya in the presence of IHP?
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