Chemistry Reference
In-Depth Information
shields it from the negatively charged side-chain of Asp103 (Figure 16.1j). It
thereby suppresses an electrostatic repulsion within the network of multiple inter-
actions, which explains the quantitative effect of its presence on lectin activity.
Extensive contacts to the carbohydrate ligand are also characteristic of the two
Ca
2+
- dependent lectins of
Pseudomonas aeruginosa
(for further details, please see
Chapter 17 ). The Gram -negative pathogen is infamous for causing morbidity and
mortality in cystic fi brosis patients as well as for being the culprit of nosocomial
infections in immunocompromised patients. As in C-type lectins, calcium ion(s)
are engaged to bind neutral sugars. The two lectins PA- IL (gene
lec
A) and PA - IIL
(gene
lec
B) target galactose and
L
-fucose, respectively (for chair conformations of
both sugars, please see Figure 1.6). PA-IL adopts a
- sandwich fold where the
contact site for galactose is at the apex [20]. The sole Ca
2+
has no notable structural
role on the protein. Its major function is to participate in the intricate network of
contacts which comprises all hydroxyl groups of galactose except for the O1 atom
[20]. Presented in the loop constituted by amino acids 100-108, the calcium ion
includes the O3/O4 atoms of the sugar ligand into its coordination sphere, the
axial hydroxyl group of galactose with its additional hydrogen bonds to the carbox-
ylate of Asp100 serving to distinguish the ' letter ' galactose from glucose/mannose
residues (Figure 16.1k). The strong involvement of the O6 atom in the bonding
network accounts for the separation of this binding mode from that of the C- type
lectins mentioned above.
Moving on to the second bacterial lectin PA-IIL, it is special among agglutinins
due to its strong binding affi nity to monosaccharides in the micromolar range (5.6
to 8.3
β
- sandwich strategically positions two
Ca
2+
. They are crucial for the high affi nity combined with a less pronounced speci-
fi city (Figure 16.1l) [20, 22, 23]. Although the jelly-roll motif defi ned above as a
frequently encountered fold is thus shared by both PA lectins, an evolutionary
relationship by divergence cannot be traced on the level of sequences. This is
refl ected, too, when analyzing the mode of sugar binding. In detail, one Ca
2+
and
a network of hydrogen bonds endow PA- IL with specifi city to galactose. In con-
trast, the two calcium ions of PA- IIL fi gure prominently in ligand contact(s) to
fucose. Amazingly, the two cations rather rigidly dock sugar ligands with equato-
rial/axial hydroxyl groups by virtue of a total of four coordination bonds: O2/O4
atoms of
L
- fucose to one Ca
2+
each and the O3 atom to both Ca
2+
, with O4, O3 and
O2 atoms of
D
-mannose being sterically equivalent to O2, O3 and O4 atom of
L
-
fucose (Figure 16.1l; please see also Figure 1.6) [22, 23]. The conspicuously high
affi nity stems from an enthalpy-driven process with no entropic penalty [21] (for
details on thermodynamics of sugar binding, please see Chapter 13.4 ). In contrast
to the pentraxins no negative charge on the ligand is required; in contrast to PA- IL
and to C-type lectins, whose affi nity for monosaccharides is in the millimolar
range, coordination bonds are established with both Ca
2+
in a topologically precise
manner. They substitute for the otherwise operative van der Waals interactions
[24] (please see also Chapter 13).
×
1 0
− 6
M) [21, 22] . Its nine - stranded
β
