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Chemical Biology 03 BLOOD. Biomolecular Structure Myoglobin and Hemoglobin 9/28-30/09. . Chemical Biology 03 BLOOD. Biomolecular Structure Myoglobin and Hemoglobin Lecture 9 and 10: 9/28-30/09. The biochemistry of O 2 binding to Hb.

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chemical biology 03 blood

Chemical Biology 03BLOOD

Biomolecular Structure

Myoglobin and Hemoglobin


chemical biology 03 blood1

Chemical Biology 03BLOOD

Biomolecular Structure

Myoglobin and Hemoglobin

Lecture 9 and 10: 9/28-30/09

the biochemistry of o 2 binding to hb

The biochemistry of O2 binding to Hb

Each of the four subunits of Hb has a central helix which binds a heme with binds an iron ion (Fe(II) which in turn binds O2.

o 2 exchanges from hemoglobin hb to myoglobin mb in the tissue


pO2 in air ~100 torrs

O2 exchanges from Hemoglobin (Hb) to Myoglobin (Mb) in the tissue



  • Oxygen binding to Hb decreases as oxygen pressure decreases.
  • Oxygen is released at the tissue, and myoglobin grabs it up.
so let s first try to understand mb

O2 Exchanges from Hb to Mb

So, let’s first try to understand Mb!!!
  • Crystal structure is very complicated.
  • Hb protein is four subunits, four heme groups, and seems to behave differently when all together as compared with monomers.
  • Oxygen saturation curve is “sigmoidal” complicated mathematical formula.
  • Crystal structure is very simple
  • Mb protein is one subunit, one heme, and behaves simply
  • Oxygen saturation curve is hyperbolic, which mathematically is quite simple y= x/(a+x)


myoglobin structure o 2 binding
Myoglobin Structure: O2 Binding
  • Mb is the oxygen storage protein in muscle
  • 153 amino acids
  • 17,000 g/mole
  • Protein has 8 helices A-H
  • Heme Fe(II) is bound through side group N of His F8 (proximal his)
  • His E7 is close to the other side of heme, but doesn’t coordinate (distal his)
myoglobin structure o 2 binding1
Myoglobin Structure: O2 Binding
  • Fe(II), iron is bound to four N atoms within heme
  • 5th coordination is N of Histidine amino acid, F8 of helix F.
  • 6th coordination site is open for O2 to bind.
  • deoxyMb, deoxyHb, heme ring is puckered in absence of 6th ligand; Fe(II) out of plane.
  • oxyMb, oxyHb ring is flat with sixth ligand bound to Fe(II), metal is in heme plane.

Proximal His

Distal His

myoglobin structure o 2 binding2
Myoglobin Structure: O2 Binding

Heme group is a really special molecule made up of carbon, hydrogen, and nitrogen, with a big fat iron atom sitting in the center waiting to bind to the O2

the biochemistry of oxygen binding

The biochemistry of oxygen binding

Here’s a cartoon of what happens when the O2 binds to the Fe in Myoglobin

myoglobin structure o 2 binding3
Myoglobin Structure: O2 Binding
  • Effect of sixth site coordination on the color of myoglobin.
  • Oxygen does not bind straight on, the N from the distal His amino acid side group in the way.

N from distal His

N from proximal His

myoglobin structure o 2 binding4
Myoglobin Structure: O2 Binding
  • Space filling model of myoglobin with His F8 coordinating and His E7 poised nearby
  • See how little room oxygen has to snuggle in and bind to the Iron.
  • Heme is bound in a hydrophobic crevice with propionic acid groups projecting into solution orienting the heme.
a tale of two binding curves

A Tale of Two Binding Curves


getting the dissociation constant from the saturation curve


sigmoidal saturation curve

two state model (T and R)

O2 binding is cooperative

myoglobin o 2 binding
Myoglobin: O2 Binding
  • What really happens in the binding (association) and unbinding (disassociation) of O2 to Mb?

Mb-O2⇌ Mb + O2

equilibrium described by the extent to which the dissociation occurs, measured by a Kd

  • We can write an equation for this equilibrium:

Kd = [Mb]free [O2] / [Mb-O2]

Kd=[Mb]free [pO2]/[Mb-O2]

[Mb]free = [Mb]T - [Mb-O2]

Kd= ([Mb]T - [Mb-O2])(pO2)


myoglobin o 2 binding1
Myoglobin:O2 Binding

Mb-O2⇌ Mb + O2 equilibrium

Kd= ([Mb]T - [Mb-O2])[pO2]


Now, just allow one more substitution and a rearrangement, and we’ll get someplace really great!

Y = fractional saturation

Y = [Mb-O2] / [Mb]T

Y = pO2 / (Kd+ pO2)

WOW, that’s a lot simpler!

hemoglobin o 2 binding
Hemoglobin: O2 Binding
  • Like Mb, Hb’s saturation decreases as pO2 decreases.
  • Unlike Mb, Hb at the same pO2, say 10 torr, Hb is much less saturated. If O2 was bound it would come off.
  • Unlike Mb, Hb binding curve is not hyperbolic, but sigmoidal.
  • Sigmoidal shape suggest two states for Hb (more on this in a minute)

Y = O2/ (Kd+ O2)

Y = O2n/ (Kd+O2n)

hb structure ab 2
Hb Structure: (ab)2
  • Hemoglobin is a dimer of dimers,a1 b1dimera2 b2
  • see
hemoglobin two states for o 2 binding
Hemoglobin: Two states for O2 Binding

T state tense

Low affinity for O2

R state relaxed

high affinity for O2

hemoglobin two states for o 2 binding1
Hemoglobin: Two states for O2 Binding

T state tense

Low affinity for O2

R state relaxed

high affinity for O2

hb describing o 2 binding
Hb: Describing O2 Binding
  • Sigmoidal binding suggests
  • Two state model: Hb can be in either
    • high O2 affinity (R state)
    • low O2 affinity (T state)
  • Binding of O2 to Hb is cooperative: binding of first ligand affects the affinity of the remaining sites for ligand.

Hemoglobin Cooperativity

R state oxy


T state deoxy