中山大学生物化学课件

need Heme prosthetic group
Heme = Protoporphyrin IX + Fe2+
liguofu
more commonly
Transition metals, Fe & Cu, have a strong
tendency to bind O2
Oxygen can be bound to a heme (2)
liguofu
Structure of Porphyrin
Methene bridge
liguofu
Pyrrole ring
Oxygen can be bound to a heme (1)
None of the aa side chains in proteins is suited for reversible binding O2
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In free heme molecules, reaction of oxygen at one of the two “open” coordination bonds of iron can result in irreversible conversion of Fe2+ to Fe3+
§4 Protein Function
§4.1 General features §4.2 Oxygen-binding proteins §4.3 Immunoglobulins §4.4 Muscle contraction
liguofu
§4.1 General features
1. Versatile in function 2. Being hard to study 3. Function via interaction
In heme-containing proteins, this reaction is prevented by sequestering the heme deep within a protein structure where acess to the two “open” coordination bonds is restricted. One of these two coordination bonds is occupied by a side-chain N of a His residue.
[L]n [L]n kd
If kd is not constant
Kd
liguofu
Quantitative description of interaction (4)
[L]n [L]n kd
[L]n
1 kd
lo1 g()nloL g] [lokg d
liguofu
Quantitative description of interaction (5)
→ Structure dynamicness of a protein is usually essential for such interactions.
liguofu
§4 Protein Function
§4.1 General features §4.2 Oxygen-binding proteins §4.3 Immunoglobulins §4.4 Muscle contraction
totalbindinsgites n[PLn]n[P]
[L]n [L]n kd
liguofu
Quantitative description of interaction (2)
[L]n [L]n kd
If kd is constant
liguofu
Quantitative description of interaction (3)
Quantitative description of Mb binding O2
[O2 ]
[O2 ] kd
kd [O2]0.5
lo1 g()nloL g] [lokg d
liguofu
The iron-porphyrin in hemoglobin accounts for the red color of blood, the copper-porphyrin in hemocyanin for blue color of blood, and the magnesium-porphyrin in chlorophyll is responsible for the green of plants.
liguofu
Quantitative description of interaction (1)
Protein + nLigand PLn
kassociantio[P[P][LLn]]n
kdisassotcioian[P[P][LLn]]n
bindinsgitesoccupied n[PLn]
liguofu
Mb has a single binding site for oxygen
His93 /F8
His64 /E7
Myoglobin:153 residues, 16700 Da
liguofu
Oxygen can be bound to a heme (3)
liguofu
NO CO
→ The interaction with other molecule (ligand) is reversible.
→ The interface between the binding site is complementary in structure, making such interaction highly specific.
Free Iron promotes the formation of highly reactive oxygen species such as hydroxyl radicals.
Coordinated N atoms help prevent the conversion of
Heme = Protoporphyrin IX + Fe2+ Fe2+ to Fe3+