Re: tryptic digest at R/K-P

Kris Gevaert (krgev@medusa.rug.ac.be)
Thu, 19 Nov 1998 13:39:47 +0100

>long time ago my supervisors teached me that trypsin does never cleave
the

>peptide-bond between LYS/ARG and PRO. Now, I also tell my students
that

>this bond is not cleaved at all. However, in a recent LC/MS analysis
we

>measured the masses of two peptides that indicated a tryptictic
cleavage

>exactly at this bond (Enzyme: mod. trypsin from Promega). Since I
could not

>believe it we additionally sequenced the peptides by Edman degradation
and

>it turned out that trypsin has cleaved the LYS-PRO bond.

>On the C-terminal side of the cleavage site there were a number of
GLY

>residues. Does anybody know if this may influences the specificity of
the

>enzyme? Were my supervisors wrong and trypsin does cleave LYS/ARG-PRO
bonds?

>

>best regards

>Petre

>

Peter,

We have seen the same phenomenon when beta-actin is digested with
trypsin (same batch as you)! With MALDI-MS,we always measure a
peptidemass of 945 da and after PSD-analysis it turns out that this
peptide has the sequence AVFPSIVGR which in the actin sequence is
followed by a proline residue and by RHQGVMVGMGQK.

I don't know whether certain amino acids may influence tryptic cleavage
at R/K-P bonds, but I have seen the same phenomenon like you did.

Kris

Kris Gevaert

Flanders Interuniversity Institute for Biotechnology (V.I.B.)

Department of Medical Protein Chemistry

K.L. Ledeganckstraat 35

B-9000 Ghent

Belgium

Europe

Tel.: +32 - 9 264 52 91

Fax: +32 - 9 264 52 79