Figure 2.
Figure 2: Putative mechanism of sulphenyl-amide formation and
subsequent reactivation. The catalytic cysteine of PTP1B (E
-SH) is oxidized to a sulphenic acid (E -S -OH). The
sulphenyl-amide may be formed by a direct mechanism involving a
nucleophilic attack of the backbone nitrogen of Ser 216 on the S
atom
of Cys 215 and subsequent release of water. Alternatively, the
sulphenic acid may be oxidized to a highly reactive intermediate
by H[2]O[2] or an oxidized thiol, which then reacts to give the
sulphenyl-amide. Reactivation of the enzyme occurs via mixed
disulphide formation with a thiol. R, glutathione or DTT; X,
leaving group OOH (sulphenoperoxoic acid) or OS(O)R
(sulphinothioic acid).
The above figure is reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2003,
423,
773-777)
copyright 2003.
atom
of Cys 215 and subsequent release of water. Alternatively, the
sulphenic acid may be oxidized to a highly reactive intermediate
by H[2]O[2] or an oxidized thiol, which then reacts to give the
sulphenyl-amide. Reactivation of the enzyme occurs via mixed
disulphide formation with a thiol. R, glutathione or DTT; X,
leaving group OOH (sulphenoperoxoic acid) or OS(O)R
(sulphinothioic acid).