Hemoglobin

1
Hemoglobin
Myoglobin
2-fold symmetric
1 O2 binding site Hyperbolic binding curve High
affinity
4 O2 binding sites Sigmoid binding curve Two
conformations Low affinity at low pO2 High
affinity at high pO2 H lowers affinity DPG
lowers affinity
Efficient transfer out
Efficient transfer in
Increased efficiency High load into body low
load out
1
2
Hemoglobin/ Myoglobin
Much greater difference between loaded and
unloaded states
2
3
Formulate a partition function
1. Two conformation states for each chain T4,
T3R, T2R2, TR3, R4 Ignore difference between a
and b
2. Two oxygenation states for each chain, with a
different site binding constant for each
conformation kb,R ? kb,T 3. Independent sites
3
4
The MWC partition function allosteric
MonodWymanChangeux
1. Two conformation states for each molecule T4,
R4 Ignore difference between a and b
2. Two oxygenation states for each chain, with a
different site binding constant for each
conformation kb,R ? kb,T 3. Independent sites
4
5
The KN partition function induced fit
Koshland Némethy Structure follows function
1. Two conformation states for each chain T4,
T3RO2, T2(RO2)2, T (RO2)3, (RO2)4 Ignore
difference between a and b
2. O2-free chain T O2-bound chain R state 3. A
single site binding constant, kb 4. Penalty for
mixed conformations
For hemoglobin Q1,2,3/ Q0 lt 1 (cooperative)
5
6
Overview of partition functions
MWC and KN share MWC only KN only
KN Anti-cooperative is a possibility MWC it is
not
6
7
Comparison of partition functions
The choice hinges on nature of poorly populated
intermediates
MWC
KN
7