Figure 7.
FIGURE 7. Model for the mechanism of inhibition of sortase
by AAEKs. Deprotonation of the carbon is conjectured
to occur via a base in the active site of sortase. This
generates enolate 13, which may be stabilized in a manner
similar to the oxyanion intermediate of sortase during catalysis
(e.g. by the guanidinium of a conserved active site arginine).
This intermediate eliminates an amine, here dimethylamine, from
the -position to generate
14. The electrophilic nature of 14 allows it to serve as an
acceptor in a Michael-type conjugate addition by the thiol of
the active site cysteine. This resulting enolate might also be
stabilized by the guanidinium moiety; subsequent protonation by
enzyme or medium would then generate the stable AAEK thioether
adduct observed.
The above figure is reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
23129-23139)
copyright 2007.
carbon is conjectured
to occur via a base in the active site of sortase. This
generates enolate 13, which may be stabilized in a manner
similar to the oxyanion intermediate of sortase during catalysis
(e.g. by the guanidinium of a conserved active site arginine).
This intermediate eliminates an amine, here dimethylamine, from
the 
-position to generate
14. The electrophilic nature of 14 allows it to serve as an
acceptor in a Michael-type conjugate addition by the thiol of
the active site cysteine. This resulting enolate might also be
stabilized by the guanidinium moiety; subsequent protonation by
enzyme or medium would then generate the stable AAEK thioether
adduct observed.