Lead is a toxic heavy metal that can be very dangerous to
humans and the environment. Lead poisoning is one of the
most common diseases caused by environmental pollution. For
rapid diagnosis and on-the-spot environmental analysis, a
simple, handy, and reliable lead detection system is a
desirable complement to conventional, instrumentally
complex laboratory methods. Researchers from the University
of Chicago and the Brookhaven National Laboratory in New
York have now presented a preliminary process for such a
quick test for lead; they have developed a fluorescent
probe that very selectively responds to lead.
Not all living things react negatively to heavy metals;
some organisms, such as bacteria, have developed
resistance. Of these bacteria, Ralstonia metallidurans is
the only type known that has a lead-specific resistance
mechanism. This is switched on whenever the bacterium finds
itself in a lead-rich environment. The bacterium must thus
have a means of detecting the lead ions. This task is
performed by a "scout" protein, called PbrR, that "keeps a
lookout" for lead ions. PbrR docks to the bacterial DNA at
a location that acts as an "on/off switch" for the lead-
resistance gene. If lead ions get into the cell, they bind
to the "scout", which then changes its form such that it
pulls the two strands of the DNA apart somewhat, switching
the gene "on".
This system is similar to that used by the research team
headed by Chuan He. However, instead of using PbrR, they
chose PbrR691, a previously functionally uncharacterized
and closely related protein that can easily be produced in
larger quantities by genetic methods. As they hoped, this
protein also recognizes lead ions. It was also necessary to
slightly alter the bacterial DNA; within the "switch"
region, the researchers replaced an adenine group with a
fluorescent analogue. Bound tight in the DNA double helix,
it does not fluoresce under normal, lead-free
circumstances. However, if a lead ion binds to PbrR691, the
two strands are locally pulled apart, which causes the
fluorescent component to protrude from the double helix and
begin to glow. The intensity of the fluorescence indicates
the lead concentration of the sample. The probe is
approximately 1000-fold more selective towards lead than
other metal ions.
"Our lead probe is a starting point for the development of
a simple, lead-specific analysis process," says He. "In
addition, we are investigating why PbrR691 binds lead ions
so selectively. This insight could help in the design of a
lead-binding antidote for lead poisoning."
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