Serine Proteases Part 5
Index to Course Material
Index to Section 12
Enzymes Index;
Part 4
Part 6
Reaction Mechanism
The model for the reaction mechanism is as follows:
(the colour scheme in the diagrams is the same as in
Part 4, i.e. catalytic triad in red, main chain hydrogen bonding groups of
the oxyanion hole white, substrate/product blue)
- Acylation step
- Firstly, the nucleophilic OG of Ser 195 attacks the carbonyl carbon
of the scissile bond, forming the tetrahedral transition state, as described in
the section on the oxyanion hole. The proton
donated from the OG atom to His 57 is then donated to the N atom of the
scissile bond, cleaving the C-N peptide bond (or C-O ester bond) to produce
the amine and the acyl-enzyme intermediate. The amine is that part of the
substrate which follows the scissile bond in the sequence; the acyl-enzyme
intermediate consists of the remaining fragment covalently bound to Ser 195.
- Deacylation step
- Secondly, the acylation step essentially occurs in reverse, but involving
a water molecule instead of the amine (which diffuses away): the water loses a
proton to His 57, and the resulting OH- nucleophile attacks the acyl-enzyme
intermediate forming another tetrahedral transition state. The proton is then
donated to the Ser OG, releasing the acid product.
Index to Course Material
Index to Section 12
Enzymes Index;
Part 4
Part 6
Last updated 11th Jul '96