In addition to the previous suggestions, if you have a metal-binding
protein, beware of acidic compounds chelating the metal and stripping it
out of the protein, as this often lead to the effect you observed as well.

Isaac
On 5 Feb 2015 13:45, "Monica Mittal" <[email protected]> wrote:

> Hi all,
> I am working to crystallize a protein-ligand complex. I did a preliminary
> melting curve analysis for the protein in the absence and presence of 2
> ligands (dissolved in protein buffer). I kept the other controls as buffer
> an a known standard to confirm instrument performance. All expts done in
> triplicates.
> Now the results are like : Tm of protein alone is 56 deg, Tm in the
> presence of Lig1 conc. of 0.05mM, 0.1mM, 1.0mM and 10.0mM is 56.2, 56.1,
> 56.0 and 53.5 respectively !! Tm in the presence of Lig 2 conc. of 0.05mM,
> 0.1mM, 1.0mM, 4.0mM and 10.0mM is 56.2, 56.1, 54.9, 52.3 and 50.6
> respectively !!
> Although the effective delta Tm for both is different at higher
> concentration, but both are kind of making protein less stable. So i was
> wondering, will it be difficult to co-crystallize them !! Any suggestions
> in this regard are highly appreciated !!
>
> Thanks
> Monica
>

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