Chemistry Reference
In-Depth Information
Sialyltransferases ST3Gal IV and VI act preferentially on type 2 substrates
(Fig. 2).
30,31
In human bronchial mucosa, ST3Gal IV is the main enzyme
for the biosynthesis of sLe
x
and 6-sulfonato-sLe
x
.
32
ST3Gal IV can also use
the core 1 structure b-Galp-(1
3)-a-GalpNAc present on O-glycans,
leading to the synthesis of sialyl
3
T antigen, whereas ST3Gal VI is also
active on glycolipids.
Within the six human a2,6-sialyltransferases that catalyze the transfer
of a sialic acid residue in a2,6-linkage to GalpNAc, three of them:
ST6GalNAc I, ST6GalNAc II and ST6GalNAc IV (Table 3) are active on O-
glycosylproteins.
27
ST6GalNAc I and ST6GalNAc II can use Tn antigen (a-
GalpNAc-(1
-
-
O)-Ser/Thr) as acceptor substrate, leading to the synthesis
of
O)-Ser/Thr) fre-
quently over-expressed in epithelial cancers and associated with cancer
aggressiveness and poor prognosis.
33
In addition, ST6GalNAc I and
ST6GalNAc II are active on T antigen (b-Galp-(1
the sTn epitope (a-Neup5Ac-(2
-
6)-a-GalpNAc-(1
-
O)-
Ser/Thr), sialylated or not.
34
When both Tn and T antigens are present,
ST6GalNAc I acts preferentially on Tn antigen, whereas ST6GalNAc II acts
preferentially on T antigen.
35
ST6GalNAc IV is only active on the sialy-
lated structure a-Neup5Ac-(2
-
3)-a-GalpNAc-(1
-
3)-a-GalpNAc linked to ei-
ther O-glycoproteins or glycolipids.
36
Finally, although preferentially
active on glycolipids G
M1b
and sialyl-lactotetraosylceramide (Neup5Ac-
(2
-
3)-b-Galp-(1
-
-
3)-b-Galp-(1
-
3)-b-GlcpNAc-(1
-
3)-b-Galp-(1
-
4)-b-Glcp-(1
-
O)-Cer),
ST6GalNAc
III
also shows
sialyltransferase
activity
towards O-
glycoproteins.
37
Among the six members of the human ST8Sia family that catalyze the
transfer of one to several sialic acid residues in a2,8-linkage to another
sialic acid of glycolipids or glycoproteins, ST8Sia-VI is the only enzyme
active on O-glycan chains (Table 3). ST8Sia VI is able to transfer a single
sialic acid residue on a2,3-sialylated O-glycans of glycoproteins leading to
the formation of diSia motifs.
38
3.2.2 Fucosylation. Fucosyltransferases are type II transmembrane
glycoproteins, localized in the trans-Golgi, catalyzing the transfer of a
terminal Fucp residue from GDP-Fucp on different types of acceptors,
including mucin O-glycan chains. a1,2-fucosyltransferases are encoded
by FUT1 and FUT2 genes, both enzymes catalyzing the transfer of a Fucp
residue in a1,2-linkage on terminal Galp residue of type 1: b-Galp-(1
-
3)-
b-GlcpNAc or type 2: b-Galp-(1
4)-b-GlcpNAc disaccharides forming the
H type 1 and H type 2 antigens, respectively, which are precursors of the A
and B blood group antigens (Fig. 2, Table 3). The expression of ABH
antigens on mucins is controlled by secretor-type a1,2- fucosyltransfer-
ase, known as the Secretor (Se) fucosyltransferase and encoded by
FUT2 gene. The A and B alleles of the ABO blood group system encode an
a1,3-N-Acetyl-galactosaminyltransferase and an a1,3-galactosyltransferase,
respectively. The a1,3-N-Acetyl-galactosaminyltransferase, or A enzyme,
transfers a GalpNAc residue from UDP-GalpNAc to H type 1 or type 2 anti-
gens, whereas the a1,3-galactosyltransferase, or B enzyme, transfers a
Galp residue to the same acceptors, generating A type 1 and type 2, or B
type 1 and type 2 antigens,
-
respectively
(Fig. 2). A family of
Search WWH ::
Custom Search