Dioxygen-carrier proteins, Heme group, Protoporphyrin IX, globin, monomeric structure, Functions, Deoxy-myoglobin and oxy-myoglobin, Oxygen Binding Curve, steric conformational changes, Spin states of iron, Differences between Hemoglobin and Myoglobin

1. U N D E R G R A D U A T E C H E M I S T R Y H O N O U R S
B I O I N O R G A N I C C H E M I S T R Y
Dioxygen Management
Protein: Myoglobin
Dr. Santarupa Thakurta
Assistant Professor in Chemistry
Prabhu Jagatbandhu College
West Bengal, India

2. Background
 Myoglobin, the first protein whose structure was
determined by X-ray crystallography, is a small
protein with relatively simple oxygen-binding
behavior.
 Its X-ray structure was determined by John Kendrew
in 1959

3. Structure of myoglobin
 The functional unit of myoglobin is an iron–porphyrin
complex that is embedded in the protein.
 The protein chain contains 153 amino acid residues
(resembles  subunit of hemoglobin).
 The molecule contains eight regions of  helix (traditionally
labeled A through H)), implying mobility.
 The single Fe porphyrin group located in a cleft between
helices E and F.
 The heme iron is five-coordinate, with the fifth ligand to the
Fe is provided by a histidine-N from helix F.
 The sixth position is the site at which O2 is may reversibly
bind.

5. O2 binding to myoglobin
 Myoglobin coordinates O2 reversibly and controls its concentration in
tissue.
 Deoxymyoglobin (Mb) is bluish red and contains Fe(II); this is the
oxidation state that binds O2 to give the familiar bright red
oxymyoglobin (oxyMb).
 The Fe in deoxymyoglobin is five-coordinate, high-spin, and lies above
the plane of the ring.
 When O2 binds, it is coordinated end-on to the Fe atom, the electronic
structure of which is tuned by the F helix histidine ligand.
 The unbound end of the O2 molecule is fastened by a hydrogen bond to
the imidazole-NH of the histidine in helix E.
 In some instances deoxymyoglobin becomes oxidized to Fe(III), which
is called metmyoglobin (metMb) and is unable to bind O2.

7. Spin states
 The coordination of O2 (a strong-field π-acceptor ligand) causes the
Fe(II) to switch from high spin (equivalent to t2g
4 eg
2) to low-spin (t2g
6 )
and, with no d electrons in antibonding orbitals, to shrink slightly and
move into the plane of the ring.
 The bonding is often expressed in terms of Fe(II) coordination by singlet
O2, in which the doubly occupied antibonding 2πg orbital of O2 acts as a
donor and the empty 2πg orbital of O2 accepts an electron pair from the
Fe.
 An alternative description is recently considered, in which the bonding is
expressed in terms of low-spin Fe(III) coordinated by superoxide, O2−.

8. O2 binding curve
 The shape of the O2-binding curve of myoglobin can be
described mathematically by the equation:
 Myoglobin’s Oxygen-Binding Curve Is Hyperbolic.
 The curve for myoglobin can be described by a simple
equilibrium between deoxy- and oxymyoglobin
 In contrast, the O2-binding curve of hemoglobin is sigmoid
(S) shaped.
 but the S-shaped curve for hemoglobin can be described
only in terms of a cooperative interaction between the four
hemes

9. The O2-Binding Curves of
Myoglobin and Hemoglobin

10. O2 Binding of Hemoglobin vs. Myoglobin
 As shown in the curves, at low oxygen pressures, the affinity of
deoxyhemoglobin for O2 is substantially lower than that of myoglobin, whereas
at high O2 pressures the two proteins have comparable O2 affinities.
 The physiological consequences of the unusual S-shaped O2-binding curve of
hemoglobin are enormous.
 In the lungs, where O2 pressure is highest, the high oxygen affinity of
deoxyhemoglobin allows it to be completely loaded with O2, giving four O2
molecules per hemoglobin.
 In the tissues, however, where the oxygen pressure is much lower, the
decreased oxygen affinity of hemoglobin allows it to release O2, resulting in a
net transfer of oxygen to myoglobin.
 The shape of myoglobin’s oxygen binding curve is hyperbolic, meaning that it
holds onto oxygen much tighter.
 Only when the amount of oxygen is extremely low, as in the mitochondria of
working muscle, does myoglobin release its oxygen.
 There, the oxygen is used in cellular respiration to produce energy.

11. Functions of Hemoglobin vs. Myoglobin
 The distinct binding curves of these two proteins
reflect their functions:
 Hemoglobin, which is well suited for oxygen binding
in the lungs, transport in the bloodstream, and
delivery to the tissues
 Myoglobin, which is well suited for oxygen storage in
the muscles and delivery to mitochondria when
needed.
Myoglobin does not exhibit co-operativity, nor Bohr effect

12. Differences between
Hemoglobin and Myoglobin