Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

Isomerases 235
rate acceleration come from transition state stabilisation A bicyclic transition
state analogue has been synthesised for the chorismate mutase reaction, as
shown in Figure 10.13. This analogue inhibits the enzymatic reaction strongly
(K i 3 mm), suggesting that the enzyme does selectively bind the transition state
of the reaction. This analogue has been used to prepare catalytic antibodies (see
Section 12.3) capable of catalysing the chorismate mutase reaction to the extent
of 10 4 -fold over the uncatalysed reaction.
The chorismate mutase enzyme from Bacillus subtilis has been crystallised in
the presence of the transition state analogue, and the X-ray crystal structure
solved (see Figure 10.14). This enzyme is a trimer of identical 127-amino acid
− O 2 C
H
Arg 90
O
O
O
CO 2
−
− O 2 C
O
CO 2
−
HN
H
N
H
O
CO 2
−
H 2 N
OH
chair-like transition state
OH
transition state analogue
OH
transition state stabilisation by Arg-90
Figure 10.13 Transition state analogue for chorismate mutase.
Figure 10.14 Structure of Bacillus subtilis chorismate mutase (PDB Wle 2CHT) trimer, with bound
transition state analogue shown in black. Arg-90 is shown in red. Each active site is at the interface
of the protein sub-units.