Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

Enzymatic Hydrolysis and Group Transfer Reactions 101
CoA-S
O
+ ROH
acyltransferase
RO
O
+ CoA-SH
Figure 5.25 Acyl transfer using acetyl CoA.
MurNAc
L-Ala
D-Glu
L-Lys
D-Ala
O
NH
D-Ala
HO
Ser-Enz
D-Ala
MurNAc
L-Ala
D-Glu
L-Lys
D-Ala
O
O
Ser-Enz
H 2 N
D-Ala
D-Ala
L-Lys
D-Glu
L-Ala
MurNAc
MurNAc
Figure 5.26 Cross-linking of peptidoglycan catalysed by d,d-transpeptidase.
L-Ala
D-Glu
O
L-Lys
D-Ala
N
H
D-Ala
D-Ala
L-Lys
D-Glu
L-Ala
MurNAc
Coenzyme A is well suited to carry out acyl transfer reactions, since thiols
are inherently more nucleophilic than alcohols or amines. Thiols are also better
leaving groups (pK a 8–9), which explains why the hydrolysis of thioesters under
basic conditions is more rapid than ester hydrolysis. Acetyl CoA is used by
acyltransferase enzymes to transfer its acetyl group to a variety of acceptors,
which can be alcohols, amines, carbon nucleophiles or other thiol groups (see
Figure 5.25). We shall encounter speciWc examples of the use of acetyl CoA in
later chapters.
Finally, there are a small number of transpeptidase enzymes that transfer
the acyl group of a peptide chain onto another amine acceptor. One important
example is the transpeptidase enzyme involved in the Wnal step of the
assembly of peptidoglycan – a major structural component of bacterial cell
walls. Peptidoglycan consists of a polysaccharide backbone of alternating
N-acetyl-glucosamine (GlcNAc) and N-acetyl-muramic acid (MurNAc) residues,
from which extend pentapeptide chains which contain the unusual
d-amino acids d-alanine and d-glutamate. The Wnal step in peptidoglycan
assembly involves the cross-linking of these pentapeptide side chains, catalysed
by a transpeptidase enzyme which contains an active site serine residue analogous
to the serine proteases (see Figure 5.26). A covalent acyl enzyme intermediate
is formed with release of d-alanine, which can either be hydrolysed to
generate a tetrapeptide side chain, or be attacked by the e-amino side chain of a
lysine residue from another chain, generating an amide cross-link. These crosslinks
add considerable rigidity to the peptidoglycan layer, enabling it to withstand
the high osmotic stress from inside the bacterial cell.