Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431

Biochemistry

Fall 2008

Lecture Notes: 29 September

© R. Paselk 2008
 
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Protein Folding, cont.

Chaperones

Myoglobin and Hemoglobin as Example Proteins

Myoglobin

Myoglobin is a 153 residue globular protein in the globin family. Eight alpha helices form its single domain (myoglobin fold) tertiary structure; about 80% alpha helix (high for globular proteins). (text Figure 5-3) Interior almost exclusively hydrophobic residues, with water excluded from interior. Surface has mix of hydrophobic and hydrophilic residues, with ionizable groups on surface.

Myoglobin functions to store and facilitate the diffusion of oxygen in muscle. Oxygen binds to a heme {Fe (II)-protoporphyrin IX} prosthetic grp (text Figure 5-1). Four of iron's six ligands are to heme nitrogens, with a fifth to a histidine nitrogen. The final ligand bond goes to oxygen. (text Figure 5-2) Breathing motions (see below) are necessary to allow the exchange of oxygen, since the heme is in a closed pocket. [overhead 8-9, 8-10, V&V]

Protein Dynamics

"Breathing" motions:

How do we know about the mobility of protein structures?
 

Oxygen Binding

Myoglobin

Let's look at binding in terms of saturation, Y, where if Y = 1 every site of every Myoglobin is occupied by an oxygen molecule (thus if Y = 0.5, then 50% of the myoglobin are binding oxygen and 50% are "empty"). Mb/Hb binding curve (text Figure 5-4b):

 

Reviewing the curve in terms of saturation, Y, if Y = 1 then every site of every Myoglobin is occupied by an oxygen molecule (thus if Y = 0.5, then 50% of the myoglobin are binding oxygen and 50% are "empty").

Can describe binding as dissociation equilibrium,then:

MbO2 Mb + O2 ; &

for saturation. Substituting, , the equation of a hyperbola. If expressed as pressures, then where P50 = pO2 @ 50% saturation. Note that the binding curve for Mb is indeed hyperbolic in shape.

Hemoglobin

Hemoglobin is an alpha-alpha-beta-beta oligomeric protein: its quaternary structure consists of a tetramer of myoglobin like subunits. (text Figure 5-6) The two types of chain are slightly shorter than myoglobin chains (alpha= 141 aa residues, beta= 146 aa residues). There are extensive contacts between an alpha and a beta subunit to give a dimer. The dimers have additional contacts to give the tetramer. Oxygen binding results in a change of conformation in Hb. (text Figure 5-10) The change of conformation affects the binding of oxygen (text Figure 5-11) {oxygen binding is reduced in the "blue" form due to steric hindrance between the oxygen and the heme}.

What about Hb oxygen binding? Obviously more complex. The sigmoid shape (s-shape) of the curve indicates cooperativity (text Figure 5-12, or see below). That is, if one site binds, another is more likely to as well (it cooperates with the first site).


Pathway Diagrams

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Last modified 30 September 2008