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Anthrax Pathway
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The pathway of the anthrax toxin can be described in
three different steps: Entry into the cell, the actions of OF, and the
actions of LF. Although it is known that these are the three main steps,
there a still many unanswered questions as to how exactly this pathway
proceeds.
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| Background |
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| Anthrax
Structure |
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The first step of the Anthrax pathway is the uptake
of the toxin into the cell. The uptake of LeTx into the cell first involves
the binding of PA to an unknown ATR. Through some type of furin-like
protease activation, PA undergoes a significant conformational change.
After this change, both EF and LF bind very tightly to PA, and the whole
system is brought into the cell via receptor-mediated endocytosis (Lacy
et all, 2002). Once inside the cell, LF and EF are released from
PA, and begin their separate pathways.
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Anthrax Pathway
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Figure 5--LeTx Entering the
Cell |
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Once inside the cell the LF is unbound from PA. The
target of LF is the second step in the cascade of MAPK. LF attacks MAPKK
in a still largely unknown manner. What is known is that LF attacks
almost the entire family of MAPKK; MKK4, MKK6 and MKK7, at the N-terminal.
However, LF does not attack MKK5. A reason for this could be the very
distant relationship this MAPKK has with teh rest of its family, as
can be seen in figure ? In addition to the MAPKK, LF also attacks MKK4,
MKK6 and MKK7. Because of its broad specificity, LF is thought to interact
with specific structural motifs to recognize its substrate and act at
full enzyme activity (Vitale et all, 2000).
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Figure 6--The MAPKK
family |
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