I want to assume that you know the basics... but just in case:
Calmodulin mediates calcium's effects on numberous chemical reactions
by sensing an elevation of free calcium ion concentration and then
activating ion-specific proteins. Therefore, Calmodulin can be seen
as an intermediary between intracellular calcium levels and specific
effector proteins that control various regulatory functions.
Now.. on to the question...
I believe the answer to the first question can (at least in part) be found here:
http://www.jbc.org/cgi/content/abstract/260/28/15100
The relevant section states that "Mercury and copper can compete with
these potentiating metal cations (calcium, La3+, Tb3+, Pb2+, or by
Cd2+) on calmodulin and produce an inactivation of this active
calmodulin conformer."
As stated, mercury serves as a competitive inhibitor for calmodulin
and therefore attaches to calmodulin's active site rather than
attaching allosterically. In a sense, then, calcium could actually
"out-compete" the competitior (mercury) and reactivate the calmodulin
conformers. It is clear, then, that the efficacy of competitive
inhibition is (at least in some sense) less than non-competitive
inhibition. Unfortunately, I couldn't not locate more specific
information on the efficacy of mercury inhibition (I'm not sure the
studies have even been done)
In response to the second part of your question, it is important to
understand the basics of competitive/non-competitive inhibition and
cooperative binding. These are basic concepts that are all over the
web... but here's a website to get things rolling
http://laplace.compbio.ucsf.edu/chem241/chp28sols.pdf
Basically, cooperative binding occurs when a calcium binds to the
active sit of calmodulin. In essence, this binding alters the
conformation of other subunits to encourge further binding. In
competitive inhibition, the competitor is, in essence, mimicking the
effect of the original ligand on calmodulin. This is, more or less,
the definition of competitive inhibition. Therefore, one would
predict that similar conformational changes would occur in calmodulin
to encourage cooperative binding.
Hope this helps. :)
--Rcubed |
