This document summarizes key information about hemoglobin and myoglobin. It discusses how hemoglobin and myoglobin were the first proteins to be crystallized and have their structures determined via X-ray crystallography. The document describes the structures of myoglobin and hemoglobin, including their subunit composition and heme groups. It explains how oxygen binding causes conformational changes in hemoglobin that result in cooperative binding and the release of oxygen in tissues.

1. Hemoglobin
By-
Saurav K. Rawat
(Rawat DA Greatt) 1

2. Hemoglobin and
Myoglobin
Because of its red color, the red blood pigment has been of
interest since antiquity.
•First protein to be crystallized - 1849.
•First protein to have its mass accurately measured.
•First protein to be studied by ultracentrifugation.
•First protein to associated with a physiological
condition.
•First protein to show that a point mutation can cause
problems.
•First proteins to have X-ray structures determined.
•Theories of cooperativity and control explain
hemoglobin function

3. The visible absorption
spectra for
hemoglobin
The red color arises from the
differences between the energy
levels of the d orbitals around the
Ferrous atom.
There is an energy difference
between them, which determines
the size of the wavelength of the
maximal absorbance band.
Fe(II) = d6 electron configuration:
Low spin state

4. The structure of
myoglobin and hemoglobin
Andrew Kendrew and Max Perutz solved the structure of these
molecules in 1959 to 1968.
The questions asked are basic. What chemistry is responsible for
oxygen binding, cooperativity, BPG effects and what alterations in
activity does single mutations have on structure and function.
Myoglobin: 44 x 44 x 25 Å single subunit 153 amino acid residues
121 residues are in an a helix. Helices are named A, B, C, …F. The
heme pocket is surrounded by E and F but not B, C, G, also H is near
the heme.
Amino acids are identified by the helix and position in the helix or by
the absolute numbering of the residue.

6. SSttrruuccttuurree ooff HHeemmoogglloobbiinn

7. MMyyoogglloobbiinn
HHeemmee
HHeemmoogglloobbiinn
2 a chains
2 b chains

9. Hemoglobin
Spherical 64 x 55 x 50 Å two fold rotation of
symmetry a and b subunits are similar and are
placed on the vertices of a tetrahedron. There is no
D helix in the a chain of hemoglobin.
Extensive interactions between unlike
subunits a2-b2 or a1-b1 interface has 35 residues
while a1-b2 and a2-b1 have 19 residue contact.
Oxygenation causes a considerable
structural conformational change

10. The Heme group
•Each subunit of hemoglobin or
myoglobin contains a heme.
•Binds one molecule of oxygen
•Heterocyclic porphyrin derivative
•Specifically protoporphyrin IX
The iron must be in the Fe(II) form or
reduced form. (ferrous oxidation) state.
Loss of electrons oxidation LEO
Gain of electrons reduction GER
Leo the lion says GER

11. 11
GLOBIN chain
HEME

12. Hemoglobin
Binding of O2 alters the structure

13. Function of the globin
Protoporphyrin binds oxygen to the
sixth ligand of Fe(II) out of the
plane of the heme. The fifth ligand
is a Histidine, F8 on the side across
the heme plane.
His F8 binds to the proximal side
and the oxygen binds to the distal
side.
The heme alone interacts with
oxygen such that the Fe(II) becomes
oxidized to Fe(III) and no longer

14. HHeemmoogglloobbiinn aanndd
mmyyoogglloobbiinn
• HHeemmoogglloobbiinn
• oxygen transport protein of red
blood cells.
• MMyyoogglloobbiinn
• oxygen storage protein of skeletal
muscles.
• As with the cytochrome example,
both proteins use heme groups.
It acts as the binding site for
molecular oxygen.

15. Hemoglobin function
a2,b2 dimer which are structurally similar to myoglobin
•Transports oxygen from lungs to tissues.
•O2 diffusion alone is too poor for transport in
larger animals.
•Solubility of O2 is low in plasma i.e. 10-4 M.
•But bound to hemoglobin, [O2] = 0.01 M or that
of air
•Two alternative O2 transporters are;
•Hemocyanin, a Cu containing protein.
•Hemoerythrin , a non-heme containing
protein.

17. Models for Allosteric
Behavior
• Monod, Wyman, Changeux (MWC)
Model: allosteric proteins can exist in two
states: R (relaxed) and T (taut)
• In this model, all the subunits of an
oligomer must be in the same state
• T state predominates in the absence of
substrate S
• S binds much tighter to R than to T

18. More about MWC
• Cooperativity is achieved because S
binding increases the population of R,
which increases the sites available to S
• Ligands such as S are positive
homotropic effectors
• Molecules that influence the binding of
something other than themselves are
heterotropic effectors

20. Myoglobin facilitates rapidly
respiring muscle tissue
The rate of O2 diffusion from
capillaries to tissue is slow
because of the solubility of
oxygen.
Myoglobin increases the solubility
of oxygen.
Myoglobin facilitates oxygen
diffusion.
Oxygen storage is also a function
because Myoglobin concentrations
are 10-fold greater in whales and

21. Fe O O Fe
A heme dimer is
formed which
leads to the
formation of
Fe(III)
By introducing steric hindrance on one side of the heme plane
interaction can be prevented and oxygen binding can occur.
The globin acts to:
•a. Modulate oxygen
binding affinity
•b. Make reversible
oxygen binding
possible

22. The globin surrounds the heme
like a hamburger is surrounded by
a bun. Only the propionic acid
side chains are exposed to the
solvent.
Amino acid mutations in the heme
pocket can cause autooxidation of
hemoglobin to form
methemoglobin.

23. When Fe(II) goes to Fe(III),
oxidized, it produces
methemoglobin which is brown
and coordinated with water in
the sixth position. Dried blood
and old meat have this brown
color.
Butchers use ascorbic acid to reduce methemoglobin to
make the meat look fresh!!
There is an enzyme methemoglobin reductase that
converts methemoglobin to regular hemoglobin.

24. Hemoglobin as oxygen
carrier
• In each hemoglobin molecule there are four
heme groups
• Heme = Fe2+ surrounded by phorphyrin
group, four N act as ligands.
• As O2 carrier: O2 binds to Fe2+ as a ligand
• Reversible process
• CO and CN– bind irreversible to Fe2+

25. OOxxyyggeenn TTrraannssppoorrtt

26. N N
eg
N N t2g
Fe2+
N
O
O
N N
Fe2+
N N
N
eg
t2g
• Changes at the Heme initiate structure switch
− DeoxyHb has Fe 0.3Å out of plane
− OxyHb has Fe in plane of porphyrin
− Fe atom pulls the bound F8 His with it
– Shifts the whole F helix, EF corner
– Salt links are broken at ab interface
– T-form becomes R-form
– R-form has greater O2 affinity
– Cooperativity set in motion
− BPG stabilizes deoxyHb T-form by creating more contacts
− O2 binding to Hb causes dissociation of BPG because the
cavity gets too small. This favors the R-form as well.

27. Quaternary structure of deoxy- and
oxyhemoglobin
T-state R-state

28. • Structural Basis for Cooperativity
• Interactions between subunits
− A dissociated Hb subunit binds O2 like Mb
− A b4 tetramer binds O2 like Mb
− Cooperativity must involve subunit interactions

29. Functions of
Haemoglobin
• Oxygen delivery to the tissues
• Reaction of Hb & oxygen
• Oxygenation not oxidation
• One Hb can bind to four O2 molecules
• Less than .01 sec required for
oxygenation
"b chain move closer when oxygenated
• When oxygenated 2,3-DPG is pushed out
"b chains are pulled apart when O2 is
unloaded, permitting entry of 2,3-DPG
resulting in lower affinity of O2

30. Oxy &
deoxyhaemoglobin

31. Oxygen-haemoglobin
dissociation curve
• O2 carrying capacity of Hb at
different Po2
• Sigmoid shape
• Binding of one molecule facilitate the
second molecule binding
•P 50 (partial pressure of O2 at which
Hb is half saturated with O2)
26.6mmHg

32. Hb-oxygen dissociation
curve

33. Hb-oxygen dissociation
curve
• The normal position of curve
depends on
• Concentration of 2,3-DPG
• H+ ion concentration (pH)
• CO2 in red blood cells
• Structure of Hb

34. Hb-oxygen dissociation
curve
• Right shift (easy oxygen delivery)
• High 2,3-DPG
• High H+
• High CO2
• HbS
• Left shift (give up oxygen less
readily)
• Low 2,3-DPG
• HbF

35. Summary
• Normal structure including the
proportion of globin chains are
necessary for the normal function of
haemoglobin
• Reduced haemoglobin in the red blood
cells due to any abnormality of any of
its constituents result into a clinical
situation called anaemia
• Metabolic & other abnormalities result
into abnormal oxygen supply to the

36. • OxyHb and DeoxyHb have very different
quaternary structures
− OxyHb is more compact (b—Febchanges from 40 to
Fe 33Å)
− When Obinds, a—b contacts change as H-bonds are
2 adjusted
− Electrostatic bonds (Salt Links) also change: OxyHb
the CO- termini can freely rotate, DeoxyHb CO-
2
2
termini salt linked
− DeoxyHb has T-form (“taut”)
− OxyHb has R-form (“relaxed”)

39. Oxygenation rotates the a1b1 dimer
in relation to a2b2 dimer about 15°
The conformation of the deoxy state is
called the T state
The conformation of the oxy state is
called the R state
individual subunits have a t or r if in the deoxy or oxy state.
What causes the differences in
the conformation states?
It is somehow associated with
the binding of oxygen, but
how?

40. The positive cooperativity of O2
binding to Hb arises from the
effect of the ligand-binding
state of one heme on the
ligand-binding affinity of
The Fe iron ains oatbhoeur.t 0.6 Å out
of the heme plane in the deoxy
state. When oxygen binds it
pulls the iron back into the
heme plane. Since the
proximal His F8 is attached to
the Fe this pulls the complete
F helix like a lever on a
fulcrum.

43. Hemoglobin
A classic example of allostery
• Hemoglobin and myoglobin are oxygen
transport and storage proteins
• Compare the oxygen binding curves for
hemoglobin and myoglobin
• Myoglobin is monomeric; hemoglobin
is tetrameric
• Mb: 153 aa, 17,200 MW
• Hb: two alphas of 141 residues, 2
betas of 146

45. Hemoglobin Function
Hb must bind oxygen in lungs
and release it in capillaries
• When a first oxygen binds to Fe
in heme of Hb, the heme Fe is
drawn into the plane of the
porphyrin ring
• This initiates a series of
conformational changes that
are transmitted to adjacent
subunits

46. Hemoglobin Function
Hb must bind oxygen in lungs
and release it in capillaries
• Adjacent subunits' affinity for
oxygen increases
• This is called positive
cooperativity

47. Myoglobin Structure
Mb is a monomeric heme protein
• Mb polypeptide "cradles" the
heme group
• Fe in Mb is Fe2+ - ferrous iron - the
form that binds oxygen
• Oxidation of Fe yields 3+ charge -
ferric iron -metmyoglobin does not
bind oxygen
• Oxygen binds as the sixth ligand
to Fe
• See Figure 15.26 and discussion

50. The Conformation
Change
The secret of Mb and Hb!
• Oxygen binding changes the Mb
conformation
• Without oxygen bound, Fe is out of
heme plane
• Oxygen binding pulls the Fe into the
heme plane
• Fe pulls its His F8 ligand along with it
• The F helix moves when oxygen binds
• Total movement of Fe is 0.029 nm -

52. Binding of Oxygen by Hb
The Physiological Significance
• Hb must be able to bind oxygen in
the lungs
• Hb must be able to release oxygen
in capillaries
• If Hb behaved like Mb, very little
oxygen would be released in
capillaries - see Figure 15.22!
• The sigmoid, cooperative oxygen
binding curve of Hb makes this
possible!

53. Oxygen Binding by Hb
A Quaternary Structure Change
• When deoxy-Hb crystals are
exposed to oxygen, they shatter!
Evidence of a structural change!
• One alpha-beta pair moves relative
to the other by 15 degrees upon
oxygen binding
• This massive change is induced by
movement of Fe by 0.039 nm when
oxygen binds
• See Figure 15.32

56. Binding of the oxygen on one heme
is more difficult but its binding
causes a shift in the a1-b2
contacts and moves the distal His
E7 and Val E11 out of the oxygen’s
path to the Fe on the other
subunit. This process increases
the affinity of the heme toward
oxygen.
The a1-b2 contacts have two stable
positions.
These contacts, which are joined
by different but equivalent sets of

57. The energy in the formation of the
Fe-O2 bond formation drives the T®
R transition.
Hemoglobins O2 -binding
Cooperativity derives from the T ®
R Conformational shift.
•The Fe of any subunit cannot move into its heme plane
without the reorientation of its proximal His so as to
prevent this residue from bumping into the porphyrin
ring.
•The proximal His is so tightly packed by its
surrounding groups that it can not reorient unless this
movement is accompanied by the previously described
translation of the F helix across the heme plane.
•The F helix translation is only possible in concert with
the quaternary shift that steps the a1C-b2FG contact
one turn along the a1C helix.

58. •The inflexibility of the a1-b1 and the a2-b2 interfaces requires
that this shift simultaneously occur at both the a1-b2 and a2-b1
interfaces.
No one subunit or dimer can change its conformation.
The t state with reduced oxygen
affinity will be changed to the r
state without binding oxygen
because the other subunits switch
upon oxygen binding. Unbound r
state has a much higher affinity for
oxygen, and this is the rational for
cooperativity

59. a. Free energy changes with
fractional saturation
b. Sigmoidal binding curve as a
composite of the R state binding and
the T state binding.

60. Binding of oxygen
rearranges the electronic
distribution and alters
the d orbital energy.
This causes a difference
in the absorption
spectra.
Bluish for deoxy Hb
Redish for Oxy Hb
Measuring the
absorption at 578 nm
allows an easy method to
determine the percent of
Oxygen bound to
hemoglobin.

61. O2 binding to myoglobin
2 2 Mb + O «MbO
Kd = [Mb][O ]
2
[MbO ]
2
[O ]
Kd [O ]
Y [MbO ]
[Mb] [MbO ]
2
2
2
2
=
O2 +
+
=
Written backwards
we can get the
dissociation
constant
Fractional Saturation solve for [MbO2]
and plug in

62. How do you measure the
concentration of oxygen?
Use the partial pressure of O2 or O2
tension = pO2
= 2
P= the partial
50 Y pO 2 +
O K pO
d 2
oxygen pressure
when YO2 = 0.50
2
Y pO 2 +
O P pO
50 2
=
What is the
shape of the
curve if you plot
YO2 vs. pO2
What does the value of P50 tell you
about the O2 binding affinity?

63. P50 value for myoglobin is 2.8 torr
or
1 torr = 1 mm Hg = 0.133 kPa
760 torr = 1 atm of pressure
Mb gives up little O2 over normal
physiological range of oxygen concentrations
in the tissue
i.e. 100 torr in arterial blood
30 torr in venous blood
YO2 = 0.97 to YO2 = 0.91
What is the P50 value for Hb?
Should it be different than myoglobin?

65. The Hill Equation
E = enzyme, S = ligand, n= small
number
E + nS « ESn This is for binding
of 1 or more ligands
Ois considered a
2 ligand
n
[ESn]
K [E][S]
= 1.
Ys n[ESn]
n([E] +
[ESn])
2. =
Fractional Saturation =
bound/total

66. As we did before, combine 1. + 2. = 3.
n
[E][S]
K
Ys n
( +
)
K
[E] 1 [S]
=
n
Ys [S]
3.
or n
+
K [S]
=
Look similar to Mb + O2 except for
the n

67. Continuing as before:
( )n
K = P50
( )
( ) ( )n
2
Y pO 2 n
+
50
n
2
= 4.
O P pO
n = Hill Constant, a non integral parameter
relating
Degree of Cooperativity among interacting
ligand-binding sites or subunits
The bigger n the more cooperativity (positive
value)
If n = 1, non-cooperative
n < 1, negative cooperativity

68. Hill Plot
Rearrange equation 4.
Log Ys = - ÷øö çè
nLog[S] logK
1-Ys
æ
y = mx + c
n = slope and x intercept of
-c/m

70. Things to remember
Hb subunits independently compete for O2 for
the first oxygen molecule to bind
When the YO2 is close to 1 i.e. 3 subunits are
occupied by O2 , O2 binding to the last site is
independent of the other sites
However by extrapolating slopes: the 4th O2
binds to hemoglobin 100 fold greater than the
first O2
A DDG of 11.4 kJ•mol -1 in the binding affinity
for oxygen
When one molecule binds, the rest bind and
when one is released, the rest are released.

71. Contrast Mb O2 binding to
Hemoglobin
YO2 = 0.95 at 100 torr
but
0.55 at 30 torr
a DYO2 of 0.40
Understand Fig 9-3
Hb gives up O2 easier than Mb and the
binding is Cooperative!!

72. 72
Oxygen and Carbon Dioxide
Transport in Blood

73. Basic Mechanism of the Gases Transportation
Two forms of the gases: physical dissolution and
chemical combination.
Most of oxygen and carbon dioxide in the blood is
transported in chemical combination
Only the gas in physical dissolution express PP and
diffuse to a place with low PP.
Dynamic balance between the two forms:
Physical dissolution P P Chemical combination
73
PP

74. 74
I. Transport of Oxygen

75. 75
Oxygen Transport
• Method Percentage
• Dissolved in Plasma 1.5 %
• Combined with Hemoglobin 98.5 %
Bound to Hgb
Dissolved

76. 76
Oxyhemoglobin Formation
• An oxygen molecule reversibly attaches to the
heme portion of hemoglobin.
• The heme unit contains iron ( +2 ) which
provides the attractive force.
O2 + Hb HbO2

77. In normal adults, most of the hemoglobin
contains 2α and 2 β chains.
Each of the 4 iron atoms can bind reversibly on
O2 molecule.
The iron stays in the ferrous state, so that the
reaction is an oxygenation, not an oxidation.
77

78. When saturated with O2 (4 O2 in one
hemoglobin molecule), it is always written
Hb4O8.
The reaction is rapid, requiring less than 0.01
second.
The deoxygenation (reduction) of Hb4O8 is also
very rapid.
78

79. Oxygen Capacity: The maximum quantity of
oxygen that will combine chemically with the
hemoglobin in a unit volume of blood;
normally it amounts to 1.34 ml of O2 per gm of Hb or
20 ml of O2 per 100 ml of blood.
Oxygen Content: how much oxygen is in the blood
Oxygen Saturation: A measure of how much
oxygen the blood is carrying as a percentage of the
maximum it could carry
79
Basic Concepts:

80. The oxygen-hemoglobin dissociation curve:
80
The curve
relating
percentage
saturation of
the O2-carry
power of
hemoglobin to
the PO2.

81. 81
The oxygen-hemoglobin dissociation curve
A. Flattened upper portion
B. Steep middle portion
C. Lower portion

82. 82
Shifting the Curve

83. Factors that Shift the Oxygen-
Hemoglobin Dissociation
Curve
83

84. 84
1. pH and PCO2: Bohr effect

85. The Bohr Effect
Competition between oxygen and H+
• Discovered by Christian Bohr
• Binding of protons diminishes oxygen
binding
• Binding of oxygen diminishes proton
binding
• Important physiological significance
• See Figure 15.34

87. Bohr Effect II
Carbon dioxide diminishes
oxygen binding
• Hydration of CO2 in tissues and
extremities leads to proton
production
• These protons are taken up by
Hb as oxygen dissociates
• The reverse occurs in the lungs

89. 89
2. Temperature

90. 3. 2,3-biphosphoglycerate, 2,3-BPG
A byproduct of anaerobic glycolysis.
Present in especially high concentration in red blood
cells because of their content of 2,3-BPG mutase.
The affinity of hemoglobin for O2 diminishes as the
concentration of 2,3-BPG increase in the red blood
cells.
90

91. 2,3-Bisphosphoglycerate
An Allosteric Effector of
Hemoglobin
• In the absence of 2,3-BPG,
oxygen binding to Hb follows a
rectangular hyperbola!
• The sigmoid binding curve is only
observed in the presence of 2,3-
BPG
• Since 2,3-BPG binds at a site
distant from the Fe where oxygen
binds, it is called an allosteric

93. 2,3-BPG and Hb
The "inside" story......
• Where does 2,3-BPG bind?
• "Inside"
• in the central cavity
• What is special about 2,3-BPG?
• Negative charges interact with 2
Lys, 4 His, 2 N-termini
• Fetal Hb - lower affinity for 2,3-
BPG, higher affinity for oxygen, so
it can get oxygen from mother

95. No BPG
O2 PRESSURE (torr)
SATURATION
1
0
10 50
With BPG
BPG Lowers the binding affinity of Hb for O2
•[BPG] = 0, Hb P50 = 1 torr
•[BPG] = 4000mM, Hb P50 = 26 torr
•Without BPG, Hb couldn’t unload O2 in cells

96. BPG acts BPG acts bbyy ssttaabbiilliizziinngg ddeeooxxyyHHbb
BPG binds by electrostatic interactions to
the highly electropositive region (red) in a
crevice between the 4 subunits
BPG binding site

97. • BPG ensures that O2 can be unloaded at the peripheral tissues
− by decreasing the affinity of Hb for O2 about 26 fold
− increasing O2, on the other hand, promotes the formation of oxyHb
whose changed conformation prevents BPG binding because the
binding cavity becomes too small
• Fetal Hb has a lower affinity for 2,3-BPG and therefore has a higher
affinity for O2
− BPG regulates O2 binding between Hb types
− This allows transfer of O2 from mother to child
− This explains the need for multiple Hb types
− If [BPG] = 0, HbA > HbF for O2 binding
− HbF has neutral Serine in place of HbA His
o2O2 PRESSURE (torr)
SATURATION
1
0
10 50
HbA
HbF
O2 flows from
mom to baby !

98. Importance:
The normal DPG in the blood …
Hypoxic condition that last longer than
a few hours…
Disadvantage:
The excess DPG also makes it more
difficult for the hemoglobin to
combines with Oin the lungs.
98
2

99. 4. Effect of Carbon Monoxide (CO)
CO combines Hb at the same point as does O,
2and can displace Ofrom hemoglobin.
2 CO binds with about 250 times as much tenacity
as O.
2Therefore, a Ponly a little greater than 0.4
CO mmHg can be lethal.
In the presence of CO (low concentration), the
affinity of hemoglobin for Ois enhanced,
99
2

100. Effect of CO & Anemia on Hb-O2 affinity
Normal blood with Hb=15 gm/dl, anemia with Hb=7.5 gm/dl,
and normal blood with 50% COHb (carboxyhemoglobin).
100

101. 101
5. Fetal Hemoglobin
Advantage
Increased O2
release to the
fetal tissues
under the
hypoxic
condition.

102. 102
II Carbon Dioxide Transport
Method Percentage
• Dissolved in Plasma 7 - 10 %
• Chemically Bound to
Hemoglobin in RBC’s 20 - 30 %
• As Bicarbonate Ion in
Plasma 60 -70 %
Dissolved
bound to Hb
HCO3-

103. 103
Carbaminohemoglobin
Formation
• Carbon dioxide molecule reversibly attaches to
an amino portion of hemoglobin.
CO2 + Hb HbCO2

104. 104
Carbonic Acid Formation
• The carbonic anhydrase stimulates water
to combine quickly with carbon dioxide.
CO2 + H2 0 H2 CO3

105. 105
Bicarbonate Ion Formation
• Carbonic acid breaks down to release a
hydrogen ion and bicarbonate.
H2 CO3 H+ + HCO-
3

106. CO2 Transport and Cl- Movement
106

107. Carbon Dioxide Dissociation Curve
107
Haldane effect
For any given PCO2,
the blood will hold
more CO2 when the
PO2 has been
diminished.
Reflects the
tendency for an
increase in PO2 to
diminish the affinity
of hemoglobin for
CO2.

108. Mechanism of Haldane effect
Combination of oxygen with hemoglobin in the
lungs cause the hemoglobin to becomes a
stronger acid. Therefore:
1) The more highly acidic hemoglobin has less
tendency to combine with CO2 to form CO2
Hb
2) The increased acidity of the hemoglobin also
causes it to release an excess of hydrogen ions
108

109. Interaction Between CO2 and O2 Transportation
1. Bohr effect
109

110. 110
2. Haldane effect

111. SSiicckkllee--cceellll aanneemmiiaa
• A Glu normally resides at position 6 of
each b- subunit. In HbS this amino is
mutated to Val
Glu 6
Glu 6
b
a
b
a
• the Val for Glu mutation makes deoxy-HbS insoluble
-findout why!

112. SSiicckkllee--cceellll AAnneemmiiaa
The Val for Glu mutation makes deoxy-HbS insoluble
In deoxy-HbS, b-subunit residues Phe 85 and Leu 88 reside at the
surface and bond with Val 6 on another b-subunit.
This leads to the formation of long filamentous strands of deoxy-HbS
and to the sickling deformation of the erthyrocytes
In oxy-HbS, b-subunit residues Phe 85 and Leu 88 do not reside at the
cell surface, so oxy-HbS does not aggregate. Thus, its oxygen binding
capacity and allosteric properties are largely retained.

113. Hemoglobin : a portrait of a soluble protein
with 4° structure A SUMMARY
Hemoglobin : a portrait of a soluble protein
with 4° structure A SUMMARY
• the heme prosthetic group is tightly bound in the protein and is
essential for function
• steric relationships within Hb ensure that the heme group has
appropriate reactivity
• hemoglobin has quaternary structure which gives it unique O2 binding
properties - allosterism and cooperativity of binding
• 2,3-bisphosphoglycerate is a regulatory molecule that stabilizes
deoxy-Hb and is essential for the allosterism and cooperativity of
binding in Hb
• there is considerable interplay between the oxygen binding affinity of
Hb and [H+], [CO2] and [2,3-BPG]
• the interplay between various sites in Hb is mediated through changes
in quaternary structure
• Sickle-cell anemia is an example of a genetically transmitted disease
which highlights the effect of one amino acid substitution on protein
structure and function

114. Rawat’s Creation-rwtdgreat@
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