Examples of protein structures
All of this work is done so that the three-dimensional structure of pro-
teins can be determined. Proteins are involved at all levels of cellular
function and an understanding of their three-dimensional structure is
required to model their function at a molecular level. For example,
proteins have the capacity to specifically bind virtually any molecule.
Enzymes play a critical role in cellular regulation and have the capacity
to specifically stabilize the transition state, which gives them tremendous
catalytic function. Myoglobin and hemoglobin have an oxygen-binding
capacity that can be very sensitive to the conditions of the circulatory
system and muscles.
Pepsin is an enzyme that digests proteins in
the highly acidic environment of the stomach.
Pepsinogen is a precursor that contains a
segment of 44 residues that are proteoly-
tically removed in the formation of pepsin.
Diffraction analysis has shown that the active
site of the precursor form is blocked by re-
sidues of the precursor segment at neutral pH
(Figure 15.20).Note that a positively charged
lysine side chain interacts electrostatically
with a pair of negatively charged aspartate
residues. When the pH is lowered, the salt
bridges are broken and the exposed catalytic
site hydrolyzes the peptide bond between the
precursor and pepsin moieties.
Myoglobin and hemoglobin are oxygen-
carrying proteins in the circulatory system
and muscles. Hemoglobin is present in the
blood and binds oxygen in the lungs, travels
through the circulatory system, and transfers
the oxygen to myoglobin in the muscles, where it is stored until needed.
In both proteins the binding of oxygen to the heme group is regulated
by the partial pressure of oxygen, as well as by pH and other factors.
The ability of proteins such as these to bind molecules can be studied
by X-ray diffraction by preparing the protein in different states. The
conformational changes that myoglobin undergoes as it binds mole-
cules is shown by the panels of Figure 15.21, which show the structures
of the heme site (seen edge on) with a bound CO molecule and the
protein after dissociation of the CO molecule. The location of the bound
CO is shown as a dark blue cylinder and a light purple cylinder after dis-
sociation. For more details on this series of experiments see Ostermann
et al. (2000).
CHAPTER 15 X-RAY DIFFRACTION AND EXAFS 335
Figure 15.20The backbone structure of
pepsinogen (light blue) showing the stabilization
of a precursor segment (brown).