: Proteoglycans and Peptidoglycans
FIGURE 11-17
Proposed mechanism for the catalytic hydrolysis of a hexasaccharide
enzyme. Glu-35 functions as a general acid catalyst do-
nating a proton to the glycosidic oxygen between sugar
residues D and E, which results in cleavage of the bond
and release of the disaccharide E-F. The remainder of the
substrate (a tetrasaccharide), however, is still bound to the
enzyme with D acquiring a positive charge (a carbonium
ion) and continuing to be in the half-chair conformation.
The negatively charged Asp-52 now stabilizes the pos-
itively charged carbonium ion intermediate. A hydroxyl
ion and a proton from water then react with the carbonium
ion and the enzyme to generate a tetrasaccharide and the
original enzyme.
In this mechanism, Asp-52 is ionized and Glu-35 is
un-ionized in the enzyme, consistent with their functions.
The optimum pH of the enzyme is 5.0 and the pH-rate
profile is bell-shaped (activity rapidly falling off on either
side of the optimum pH). At pH 5.0, Asp-52 (pK' ~3.8) is
ionized and Glu-35 (pK' ~6.7) is un-ionized. The pK' of
Glu-35 is significantly different from that of the free amino
acid (4.25) because Glu-35 is in a nonpolar region of the
molecule. Asp-52, on the other hand, is in a polar environ-
ment, where its ionization is facilitated. The importance
of acidic amino acid residues in catalysis is further sub-
stantiated by the fact that lysozyme remains active when
all carboxyl groups, except those of Glu-35 and Asp-52,
are chemically modified (e.g., by esterification).
11.3 Lectins
The lectins are a group of proteins, originally discovered
in plant seeds (now known to occur more widely), that
bind carbohydrates and agglutinate animal cells. They
have two or more stereospecific sites that bind noncova-
lently with the terminal (and often penultimate) residue
at the nonreducing end of an oligosaccharide chain. A
number of plant lectins have been purified and their
binding properties investigated. Wheat germ agglutinin
binds to N-acetylglucosamine and its glycosides; con-
canavalin A from jack beans binds to mannose, glucose,
and glycosides of mannose and glucose; peanut agglu-
tinin binds to galactose and galactosides; and red kid-
ney bean lectin binds to N-acetylglucosamine. Since
lectins have high affinity for specific sugar residues, they
have been used to identify specific carbohydrate groups
and used in the purification of carbohydrate-containing
compounds. Lectins may be involved in carbohydrate
transport, specific cellular recognition, embryonic de-
velopment, cohesion, or binding of carbohydrates. As
noted in Chapter 10, hepatocytes bind to serum glyco-
proteins with exposed galactose residues. This binding
is thought to be a lectin-mediated clearance of par-
tially degraded glycoproteins. Hepatocytes also contain a
Ca2+-dependent fucose-binding lectin. A lectin that binds
to N-acetylglucosamine- and mannose-terminated glyco-
proteins in reticuloendothelial cells has been identified.
Many lectins are glycoproteins.
Some lectins cause agglutination of red blood cells
and can be used in typing of blood groups. Soybean
lectin, a galactose-binding protein, binds selectively to
T lymphocytes and causes their agglutination. Thus, it
has been used in selective removal of mature T lym-
phocytes from bone marrow preparations. In treatment
of disorders such as immunodeficiencies, blood cancers,
and some hemoglobinopathies, bone marrow grafts are
made after ensuring that donor and recipient are histo-
compatible. If they are not, the donor cells destroy the
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