On Wed, Mar 31, 2010 at 5:57 PM, Muhammed bashir Khan <
[email protected]> wrote:

> I am working with protein which are supposed to be bound with Magnesium
> and Cobalt metals.I have now its crystals which are diffracting quite
> nicely.I want to know the Magnesium and Cobalt binding residues in the
> target protein.  When I add magnesium or Cobalt salts to protein  solution
> even 1mM about 50 percent of the protein precipitated out.


Sometimes this doesn't matter.  I used to work with a protein that partially
precipitated when I added 2mM manganese (the physiological metal ion), but I
just spun down the solution at top speed in a microcentrifuge and continued.
 The purification yield was always high enough that I still had plenty left
for trays (and if you have a Mosquito robot or the equivalent, just 8
microliters is enough), and whatever stayed in solution was still easy to
crystallize.  You might need to re-concentrate, however.

An alternate solution would be to co-purify with 1mM magnesium in all
buffers (may or may not work, but it can't hurt to try).  I don't know
whether this is feasible using cobalt - are the metals interchangeable, or
does your protein really bind two distinct sets of ions?  Cobalt has the
advantage of being much larger than water and has an easily measurable
anomalous signal, but magnesium is usually obvious from the coordination
geometry (and in my experience it tends to have a much lower B-factor too),
and usually gentler towards proteins.

-Nat

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