Download 1-Structure of Heme

Structure of Heme
Dr. Shumaila Asim
Lecture # 1
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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.
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Heme is a complex of protoporphyrin IX and ferrous iron (Fe2+)
Hemoproteins
• Hemoglobin (Hb)
• Myoglobin (Mb)
• Cytochromes
• Catalases (decomposition of 2
H2O2 to 2 H2O and O2)
• Peroxidases
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
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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
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Globin of hemoglobin is a globular protein with a
quaternary structure
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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
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Hemoglobin
 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
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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.
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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
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
Properties of iron in heme
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
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
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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.
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The distal histidine acts as a gate that opens and closes as O2 enters the hydrophobic
pocket to bind to the heme
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
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