This colorful image was computer generated at Argonne National Laboratory's
Structural Biology Center (SBC). It is being used to aid researchers develop
strategies to combat cholera.
Disease-carrying organisms and molecules attack by physically attaching to
cells. By knowing the physical structure of the part that attaches, scientists
can design drugs that latch onto the disease-carrier in the same place, thus
blocking its ability to attack healthy cells. This make medication more effective
and less likely to create side effects. Researchers prefer to use this drug-design
technique rather than the trial and error methods used in the past.
The cholera structure determined at Argonne National Laboratory's Structural
Biology Center (SBC) by Rongguang Zhang is one example of how structure provides
important insight.
Cholera causes diarrhea that can rob the body of 60 percent of its weight
in a single day. It is caused by the bacterium Vibrio
Cholerae. This
bacterium thrives in the small intestine where it produces a toxin that induces
the bowel lining, the epithelium, to secrete massive amounts of water.
Cholera toxin binds to a specific receptor protein on the surface of the
epithelial cells. Once bound, the cell swallows the cholera toxin, and its enzyme
is released into the cell. The three-dimensional SBC image shows the cholera
toxin to be shaped like a five-sided inner tube that attaches to the outside of a
cell. Researchers believe the enzyme enters the cell through the inner-tube's
center opening. Inside the cell, the toxin turns on the pump to push water into
the bowel causing debilitating diarrhea.
When researchers saw that the enzyme only pierces the cell but does not
destroy it, they understood that healthy cells would naturally replace infected
cells after their normal five-day lifespan. In other words, if the victim can
survive the diarrhea, he or she can survive the cholera.
