CLINICAL CASES
11
Definitions
Allosteric effectors:
Molecules that bind to enzymes or protein carriers at
sites other than the active or ligand binding site. On binding, allosteric
effectors either positively or negatively affect the enzymatic activity or
capability of the protein to bind its ligand.
Globin:
The globular proteins that are the polypeptide components of myo-
globin and hemoglobin. They contain a hydrophobic pocket that holds
the heme prosthetic group.
Globin fold:
The three-dimensional structure of the proteins that is com-
mon to myoglobin and the subunits of hemoglobin.
Heme:
A porphyrin ring that has a Fe+2 ion coordinately bound in the cen-
ter of the molecule. Heme binds oxygen in hemoglobin and myoglobin
and serves as an electron carrier in the cytochromes.
Hemoglobin:
The tetrameric protein in high concentration in red blood
cells that binds oxygen in the capillaries of the lungs and delivers it to
peripheral tissues. Each globin subunit contains a heme group that binds
oxygen when the iron atom is in the ferrous (+2) oxidation state.
Myoglobin:
A protein having a single globin polypeptide with a bound
heme group. It is located primarily in muscle cells and stores oxygen for
times when there is a high demand for energy.
Protein primary (I
°
) structure:
The amino acid sequence of the protein,
listed from the amino-terminal amino acid to the carboxy-terminal amino
acid.
Protein secondary (II
°
) structure:
The local three-dimensional spatial
arrangement of amino acids close to one another in the primary
sequence. a-Helices and P-sheets are the predominant secondary struc-
tures in proteins.
Protein tertiary (III
°
) structure:
The overall three-dimensional structure
of a single polypeptide chain, including positions of disulfide bonds.
Noncovalent forces such as hydrogen bonding, electrostatic forces, and
hydrophobic effects are also important.
Protein quaternary (IV
°
) structure:
The overall three-dimensional arrange-
ment of polypeptide subunits in a multi-subunit protein.
DISCUSSION
The
activity
of a given protein is dependent on
proper folding
of its polypep-
tide chain to assume a defined
three-dimensional structure.
The importance
of protein folding to molecular medicine is emphasized by the fact that many
disease-causing mutations do not directly affect the active or ligand binding
site of proteins, but instead cause
local or global alterations in protein struc-
ture
or
disrupt the folding pathway
such that the native protein fold is not
achieved, or undesirable interactions with other proteins are promoted. The
molecular defect that changes adult hemoglobin (HbA) to sickle hemoglobin
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