Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

206 Chapter 8
Glyphosate
H
H
N
CO −
2
2− PO 3
EnzB
Transition state
H
H H
R
δ−
O
H
δ+
CO −
O 2
PO 2−
3
Figure 8.21 Inhibition of EPSP synthase by glyphosate.
animals as they do not utilise the shikimate pathway and hence have to consume
the aromatic amino acids as part of their diet. Since glyphosate is non-toxic and
remarkably bio-degradable (by enzymes which cleave carbon–phosphorus
bonds!), it represents an ‘environmentally friendly’ herbicide. How does it inhibit
EPSP synthase It is thought that the protonated nitrogen of glyphosate mimics
the transition state for attack of shikimate-3-phosphate upon PEP. It is likely
that signiWcant positive charge accumulates in this transition state on C-2 of
PEP, as shown in Figure 8.21.
There is only one other example of an enolpyruvyl transfer reaction, the
conversion of UDP-N-acetyl-glucosamine to enolpyruvyl-UDP-N-acetylglucosamine,
involved in bacterial cell wall peptidoglycan biosynthesis. The
transferase enzyme responsible for this transformation has been puriWed, overexpressed,
and analysed by similar approaches. A tetrahedral intermediate has
been found for this enzyme also, although there is evidence that PEP forms a
reversible adduct with an active site cysteine residue. A mechanism for this
enzyme is shown in Figure 8.22.
OH
2− O 3 PO
CO 2
−
CH
EnzS − 3
CO −
EnzS
2 +
OPO 2−
3
reversible
PEP adduct
HO
HO
O
NHAc
OUDP
UDP-N-acetyl-glucosamine
OH
OH
HO
O
CO 2
−
O
NHAc
OUDP
H 3 C
2− O 3 PO
HO
O
CO 2
−
O
NHAc
OUDP
tetrahedral intermediate
Figure 8.22 Reaction catalysed by UDPGlcNAc enolpyruvyl transferase.