Serine Proteases Part 5
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)
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Acylation step
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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.
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Deacylation step
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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.
Last updated 16th April '97