1. Dr. Shumaila Asim Lecture # 1
Structure of Heme
Dr. Shumaila Asim
Lecture # 1

2. Hemoproteins
Hemoproteins are a group of specialized proteins that contain heme as a tightly bound prosthetic group.
Heme is a complex of protoporphyrin IX and ferrous iron (Fe2+) .
The iron is held in the center of the heme molecule by bonds to the four nitrogens of the porphyrin ring.

3. Heme is a complex of protoporphyrin IX and ferrous iron (Fe2+)

4. Hemoproteins
Hemoglobin (Hb)
Myoglobin (Mb)
Cytochromes
Catalases (decomposition of 2 H2O2 to 2 H2O and O2)
Peroxidases

5. Globular proteins
Amino acid chains fold into shapes that resemble spheres are called globular proteins
This type of folding increases solubility of proteins in water
Polar groups on the protein’s surface
Hydrophobic groups in the interior
Fibrous proteins are mainly insoluble structural proteins

6. Four Levels of Protein Structure
Primary, 1o
the amino acid sequence
Secondary, 2o
2-D arrangement of backbone atoms in space
Tertiary, 3o
3-D arrangement of all the atoms in space
Quaternary, 4o
3-D arrangement of subunit chains

7. Globin of hemoglobin is a globular protein with a quaternary structure

8. Globular proteins Hemoglobin: oxygen transport function
Myoglobin: oxygen storage/supply function in
heart and muscle
α1, α2, β-globulins: various functions
γ-globulins (immunoglobulins): immune function
Enzymes: catalysis of biochemical reactions

9. Hemoglobin Contains two dimers of αβ subunits
A major globular protein in humans
Composed of four polypeptide chains:
Two α and two β chains
Contains two dimers of αβ subunits
Held together by non-covalent interactions
Each chain is a subunit with a heme group in the center that carries oxygen
A Hb molecule contains 4 heme groups and carries 4 molecules of O2

11. Heme is the prosthetic group of hemoglobin, myoglobin, & cytochromes
Heme is the prosthetic group of hemoglobin, myoglobin, & cytochromes. Heme is an asymmetric molecule. E.g., note the positions of methyl side chains around the ring system.

12. Heme structure Heme is a metaloporphyrine (cyclic tetrapyrrole)
Heme contains:
conjugated system of double bonds → red colour
4 nitrogen (N) atoms
1 iron cation (Fe2+) → bound in the middle of tetrapyrrole skelet by coordination covalent bonds
methenly bridge pyrrole ring

13. Properties of iron in heme
Coordination number of iron in heme = 6
6 bonds:
4x pyrrole ring (A,B,C,D)
1x link to a protein
1x link to an oxygen

14. Properties of iron in heme

15. Myoglobin (Mb)
is a single-chain globular protein of 153 AA, containing 1 heme group
transports O2 in skeletal and heart muscle
is found in cytosol within cells
is a marker of myocard damage

17. Iron Iron can bind in the center of the four rings.
Fe is in the ferrous state (Fe2+) can form 6 bonds:
4 with the nitrogen of the rings,
One (known as the fifth coordinate) with the nitrogen of a histidine imidazole (known as proximal His).
One with O2 (the sixth coordinate)
Oxidation of iron to the Fe3+, ferric, state makes the molecule incapable of normal O2 binding

18. Structure-function relationship
The planar heme group fits into a hydrophobic pocket of the protein and the myoglobin-heme interaction is stabilized by hydrophobic attractions.
The heme group stabilizes the tertiary structure of myoglobin.
The hydrophobic interior of myoglobin (or hemoglobin) prevents the oxidation of iron, and so when O2 is released, the iron remains in the Fe(II) state and can bind another O2.

19. The distal histidine acts as a gate that opens and closes as O2 enters the hydrophobic pocket to bind to the heme

20. Structure of heme prosthetic group
Two hydrophobic side chains on O2 binding site of heme help hold it in place
oxygenation changes state of Fe
Purple to red color of blood, Fe+3 – brown
Oxidation of Fe+2 destroys biological activity of myoglobin
Physical barrier of protein is to maintain oxidation state of Fe+2