Phosphorylation of methionine sulfoximine by glutamine synthetase.

Abstract

Ovine brain glutamine synthetase interacts with methionine sulfoximine, ATP, and Mn++ (or Mg++) to yield an inhibited enzyme which contains close to 8 moles each of methionine sulfoximine phosphate and ADP. The occurence of this phosphorylation reaction is in accord with previous findings that indicate formation of enzyme-bound [gamma]-glutamyl phosphate as an intermediate in the reactions catalyzed by glutamine synthetase. The tight binding of methionine sulfoximine phosphate and ADP to the enzyme may explain the irreversible inhibiton produced by methionine sulfoximine in vitro and in vivo. Methionine sulfoximine phosphate is released by heat denaturation of the enzyme or by precipitation of the enzyme with perchloric acid. Methionine sulfoximine phosphate is split to methionine sulfoximine and inorganic phosphate when heated in 6 N HCl at 100[degree] for 2 hr, or when treated at 37[degree] with alkaline phosphatase.