Re: tryptic digest

Deb McMillen (mcmillen@morel.uoregon.edu)
Wed, 25 Feb 1998 09:51:59 -0800 (PST)

Paul, Thanks for your reply.
I've talked to my client about the acid--often trypsin is reconstituted
in dilute acid to keep it active during storage. There wasn't any acid
added at any step--he didn't even boil the samples prior to loading on the
gel to avoid elevated temperatures with the Tris to keep it's pH right.
BUT I do have him searching for the source of acid conditions.

Another idea, given by Lowell Erickson, is that this protein is already
cleaved during isolation--it is obtained by over expression in E coli--but
is held together by di-sulfide bonds. It runs as one band on a denaturing
gel, so we doubt this is the case, but we are going to through it in the
N-terminal sequencer and see if the first cycle shows two free N-terminii.

Deb

On Wed, 25 Feb 1998, Paul Jedrzejewski wrote:

> Hi Deb,
>
> Perhaps the DP cleavage occurs after you have performed your digest.
> Are you stopping the digest with 10%TFA, or running HPLC with 0.1%TFA?
> good luck,
> Paul
>
>
> Deb McMillen wrote:
>
> > Hi, all,
> > I have a client who is getting cleavage of a protein between D and P with
> > trypsin (Sigma Type 13 TPCK treated bovine pancreatic). When he starts
> > the cleavage, the protein is intact. Of course, the first thing that
> > comes to mind is how labile the DP bond is, but doesn't it take at least
> > acidic conditions perhaps with elevated temperature to break the bond?
> > The tryptic digestion (partial) is done at room temperature in 10 mM
> > Hepes, 150 mM NaCl, 0.1 mM EDTA, 0.5mM DTT, 10% glycerol pH 7.8. They are
> > using 50 micrograms of trypsin per 500 micrograms of protein. Is
> > one of the reaction mixture components a strong (or weak) enough acid to
> > attack the DP bond? This morning they are checking the pH of the
> > reaction mixture--the typsin is reconstituted in water before addition to
> > the protein in 10mM Hepes (not much buffering capacity) at pH 7.8, but it
> > has always been 7.8 before.
> >
> > Thanks for any suggestions, Deb
> >
> > Deb McMillen
> > Institute of Molecular Biology
> > University of Oregon
> > Eugene OR 97403
>
>
> --
> --------------------------------
> Paul Jedrzejewski, Ph.D.
> Barnett Institute
> Boston, MA 02115
>
> voice 617.373.2857
> fax 617.373.2855
>
> http://www.barnett.neu.edu
> -------------------------------
>
>