Chemistry Reference
In-Depth Information
protein structure
Figure 8.4
Structure of myoglobin (Protein Data Bank; DOI: 10.2210/pdb1mbn/pdb) and detail of the heme of
hemoglobin.
2
2
heterotetramer, meaning there are pairs of two classes of polypeptide chains in the proteins,
each containing one heme unit that each bind dioxygen. In both myoglobin and hemoglobin,
the oxygen binds to an iron(II) centre bound covalently also to the four N-donors of a
porphyrin, which is an aromatic 16-membered tetraaza-macrocycle. The porphyrin is an
easily-built compound in chemistry. In nature, the heme is assembled from precursor com-
ponents that leave substituents on the macrocycle ring of the heme (Figure 8.4). The heme
in hemoglobin is embedded in a protein crevice where it is surrounded by hydrophobic
groups, and where the Fe(II) is covalently bonded at one axial site by close approach of one
imidazole group nitrogen that is part of a histidine amino acid residue (called the
'proximal'
histidine) of a protein chain. Another imidazole nitrogen is located near the other 'empty'
axial site, approaching but not achieving a bonding distance (this is called the
'distal'
histidine); it is at this protected site that dioxygen coordinates as a monodentate ligand,
taking the iron(II) from a five-coordinate to a preferred six-coordinate octahedral complex
without oxidizing the metal centre. Only the coordinate bond from the proximal histidine
to the iron binds the heme to the protein; if this bond is broken, the small heme unit can be
removed from the protein. Degradation is initiated by this Fe N bond breaking, which is
followed by release and destruction of the heme, accomplished by special
oxygenase
and
reductase
enzymes.
The role of the protein 'pocket' in which the heme unit sits in hemoglobin is twofold. It
provides a water-resistant hydrocarbon-based environment of low dielectric constant that
is unsuited to highly ionic character in the heme. This leads to the redox potential for
the Fe(II)/(III) couple being altered sufficiently to make oxidation impossible by available
biological oxidants. Thus dioxygen can bind, but will not oxidize the iron centre. The
severe steric constraints imposed by the heme environment means that it is also impossible
for another heme iron centre to approach the embedded heme, thus prohibiting unwanted
formation of stable oxidized bridging oxygen-linked dimers of the form Fe
III
is found in red blood cells. It is a larger and more complicated protein, referred to as an
O
2
−
Fe
III
.
