Re: Protein sequencing: retention time of oxidized methionine

Deb McMillen (mcmillen@morel.uoregon.edu)
Fri, 8 Jan 1999 10:32:22 -0800 (PST)

Rod, I was wondering if there are mets that are so buried or in a
microenvironment (I love that term) that CNBr cannot attack them--even
though they are met and not met sulfoxide. I've always understood that
CNBr maps of proteins were most likely not going to be complete--but is
that only dependent on the presence of met sulfoxide sites?
Thanks,
Deb McMillen
Institute of Molecular Biology
University of Oregon
Eugene OR

On Thu, 7 Jan 1999, Rod Levine wrote:

> At 10:14 AM 1/7/99 -0800, Suzanne Perry-Riehm wrote:
> >Does anyone have any experience with the retention time of oxidized
> >methionine? I run a PE-ABI 476A and have a client interested in elucidation
> >of MET and it's oxidized form. Thanks in advance.
> >
> Suzanne,
>
> Straight Edman sequencing won't work for locating the sites of methionine
> sulfoxide (which is the form I'm assuming your client is interested in since
> the sulfone rarely occurs). That's because the sulfoxide is reduced back to
> methionine during the Edman reactions. A similar reduction is well known to
> occur during acid hydrolysis for amino acid analysis, which is why you can't
> quantitate methionine sulfoxide in proteins by simple amino acid analysis.
>
> However, if you or your client are willing to add the simple step of cyanogen
> bromide treatment, then you can probably get the information you want. CNBr
> will oxidze methionine to homoserine, with cleavage of the following peptide
> bond. However, methionine sulfoxide is not affected by CNBr. You may have to
> repurify the peptide(s) of interest after the CNBr treatment, and then proceed
> onto the sequencer. The methionine sulfoxide will be reduced back to
> methionine, which will elute at the normal PHT-Met position.
>
> For an alternative approach to locating methionine sulfoxde in proteins with a
> sequencer, consider "simultaneous sequencing" of a peptide mixture. See PNAS
> 93:15036-15040, 1996.
>
> Rod Levine
>
>
>
> NIH
> Bldg 3, Room 106 MSC 0320
> Bethesda, MD 20892-0320
>
> email: rlevine@nih.gov
> voice: 1 (301) 496-2310
> fax: 1 (301) 496-0599
>