Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

236 Chapter 10
sub-units. Each sub-unit contains Wve strands of b-sheet and two a-helices. The
b-strands of each sub-unit pack together to form the trimer structure, with
active sites at the interface of each pair of sub-units.
Examination of the active site structure has revealed that the ether oxygen of
the analogue lies within hydrogen-bonding distance of the guanidinium side chain
of Arg-90, as shown in Figure 10.13. Molecular modelling studies on the enzyme–
substrate and enzyme–transition state complexes have revealed that Arg-90 can
form a favourable electrostatic/hydrogen-bonding interaction with the transition
state. This interaction and other transition-state binding appear to provide suYcient
stabilisation to account for the 10 6 -fold rate acceleration. This type of
electrophilic catalysis is precedented in synthetic organic chemistry in the form
of Lewis acid catalysis of pericyclic reactions such as the Claisen rearrangement.
There is one additional class of isomerisation reactions, the vitamin B 12 -
dependent skeletal rearrangements, which will be described in Section 11.2,
since they involve radical chemistry.
Problems
(1) 2,6-Diaminopimelic acid is a naturally occurring amino acid involved
in the biosynthesis of l-lysine. SS-Diaminopimelate is converted to RSdiaminopimelate
by a cofactor-independent epimerase enzyme, and
RS-diaminopimelate is then decarboxylated to l-lysine by a PLP-dependent
decarboxylase. What product would you expect if these two reactions were
carried out consecutively in 2 H 2 O
HO 2 C
CO 2 H
NH 2 NH 2
2,6-diaminopimelic acid
(2) The following reactions are part of a pathway for degradation of phenol in
Pseudomonas putida. Suggest a mechanism for the isomerase reaction. This
organism is found to degrade 2-chlorophenol quite readily. What do you
think the fate of the additional chlorine atom is
OH
OH
OH
CO −
2
CO −
2
CO 2
−
O
O
isomerase
CO − CO − CO − CO −
2
2
2
2 O
+
O
CH 3 CO −
CO −
2
2
O