Gene Cloning

238 Gene Cloning
once the structures have been resolved they are deposited as a series of
coordinates in one of the structural databases and these can be displayed
in three-dimensions on a desk-top computer using free software such as
Chime or Rasmol. Where three-dimensional structures are available you
will see links from SwissProt entries and BLAST search outputs. Even where
there is no structure available for a particular protein it is possible to model
the structure if a homologous sequence can be found for which a structure
is available, although this is really a job for the experts.
The power of comparing three-dimensional structures rather than
sequences is demonstrated by returning to the example of the serine proteases.
The trypsin-like serine proteases are composed largely of β sheets
(Figure 8.16a). There is another class of serine proteases, which are found
mainly in bacteria, called the subtilases. These enzymes are very different
in overall structure from the trypsin family enzymes, being mostly composed
of α helices (Figure 8.16b). However, like the trypsin family enzymes,
their catalytic activity is provided by the catalytic triad of serine, histidine
and aspartate. The sequence around the amino acids of the catalytic triad
is different in the two proteins and you would not detect the subtilases
using a profile or pattern derived from the trypsin family. However, the two
different protein structures bring the amino acids of the catalytic triad into
almost exactly the same positions in three-dimensional space, creating
conditions for the same catalytic mechanism to operate. Comparing the
(a)
(b)
Figure 8.16 Three dimensional structure of serine proteases. a) Chymotrypsin, this
member of the trypsin-like family of serine protease is largely composed of β sheets. b) Subtilisin
from Bacillus subtilis; this bacterial serine protease is largely composed of α helices.