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