Biology Reference
In-Depth Information
two vacant positions remain. In myoglobin, a globin protein molecule
occupies one of the two positions. The remaining position can bind
an O
2
molecule, so myoglobin could be thought of as a monomeric
oxygen-binding heme protein. Hemoglobin, on the other hand, is a
tetramer: it contains four protein subunits,
a
2
b
2
, each similar to
myoglobin, each with its own heme. Because each hemoglobin subunit
can bind an O
2
molecule, the tetramer can bind up to four O
2
molecules
at a time. Figure 7-2 shows the three-dimensional hemoglobin structure
determined by John Kendrew (1917-1997) and Max Perutz (1914-2002).
In 1962, they shared a Nobel Prize in Chemistry for this work.
Heme
Heme
The ferrous ion in the deoxygenated hemoglobin is situated slightly to
one side of the plane of the other heme atoms. When an O
2
molecule is
attached, a new geometry arises in which the ferrous ion becomes
coplanar with the rest of the heme. This causes a change increasing O
2
affinity and making consecutive oxygenation easier. This effect is called
cooperativity. Figuratively speaking, as the process repeats, the whole
macromolecule pulsates like a heart, the ferrous ion wobbling to and fro
across the heme plane. The cooperative binding of O
2
results from
molecular interactions at many levels: the movement of the iron in the
heme, structural changes within the individual subunits, and a
reorientation of the subunits within the tetrameric hemoglobin.
Hemoglobin, therefore, is not just a simple mix of four independent
oxygen-binding subunits but, rather, a ''molecular machine'' with its
structure directly related to its O
2
transport function.
Heme
Heme
FIGURE 7-2.
Structure of the complete hemoglobin protein.
The polypeptide chains of the four subunits are
given in the form of coiled ribbons. The small
spheres linked together are the atoms within
the heme. The whole hemoglobin complex is
globular (i.e., the polypeptide chains are coiled
to an almost spherical configuration).
As hemoglobin-oxygen binding is just one of many binding reactions
that occur in living organisms, we now examine some concepts
fundamental to this larger class of molecular interactions.
II. BINDING REACTIONS
Binding reactions are the most common types of molecular interactions
taking place within living organisms. A binding reaction occurs when
two or more molecules prefer each other's company more than the
company of other molecules within a solution. Put simply, if we could
look with a very high-powered microscope, we would find the bound
molecules had a higher probability of being together than would be
predicted by a random distribution of all the molecules within the
solution. Binding reactions are common in almost all fields of chemistry,
biochemistry, medicine, physiology, and physics. For example, in
pharmacology the simple mechanism of drug action is for a drug to bind
reversibly to a specific receptor to form a drug-receptor complex, initiating
an effect that is usually proportional to the concentration of the complex.
Symbolically, this process could be expressed as:
½
Drug
þ½
Receptor
$½
Drug-Receptor
!
Effect
;
(7-1)
