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Figure 5.
(A) Overlay of LT1009 and Q425 anti-CD4 antibody Fab crystal
structures illustrates their overall homology and different
Ca^2+ binding sites. LT1009 is colored as in previous figures
while the Q425 light chain is cyan and the heavy chain fragment
is blue. For the sake of clarity, S1P has been removed from the
LT1009 Fab model. (B) A close up view of Ca^2+ binding sites in
the 2 models reveals conservation of metal coordinating side
chains and the different conformations of CDR-H3. (C) Schematic
representation of a possible mechanism of S1P binding by LT1009.
In its unbound conformation, the light chain (labeled “L” in
the figure) binds one Ca^2+ at a site similar to that observed
in the Q425 antibody structures. S1P binding introduces
conformational changes that disrupt the original Ca^2+ binding
motif as well as potentially introducing one additional Ca^2+.
The phosphate group of S1P then combines with 2 Ca^2+ to produce
the extremely stable Ca^2+ coordination complex observed in the
S1P:LT1009 Fab complex crystal structure.
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