Methionine oxidation: effects on tryptophan?

Henry Keutmann (keutmann@helix.mgh.harvard.edu)
Fri, 15 Jan 1999 13:30:57 -0500

We are studying the effects of methionine oxidation on the function of
a protein that also contains tryptophan. Following conversion of Met
to the sulfoxide by means of hydrogen peroxide (1:50), we find upon
sequence analysis that tryptophan has been largely replaced by an
derivative eluting earlier, just before proline, from our ABI 477
system (time 19.03 min, compared with Pro 19.93, DPTU 23.33,
<underline>bona</underline> <underline>fide</underline> tryptophan
24.95 min on the usual NaAcetate/ isopropanol/acetonitrile gradient).
Tryptophan appears normal in control preparations incubated with
solvent alone (.1% TFA pH 2.0, 37 deg, 45 min).

Reports I've found, dating back a long time, indicate that tryptophan
is not affected by these oxidation conditions. Has anyone seen this
derivative, and if so does it represent serious damage or modification
prior to sequencing?

Thanks very much for any suggestions!

Henry T. Keutmann, MD

Endocrine Unit, Massachusetts General Hospital

Boston MA 02114

Tel. 617-726-3966

Fax 617-726-7543

Email Keutmann@helix.mgh.harvard.edu