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Figure 1.
Fig. 1. A: Structure-basedsequencealignment of C-typelectin
domains fP-selectin andthemannose-bindingprotein(MBP).
Secondary-structureelments in MBP arelabeled.Residuescon-
servedin MBP and P-slectin are boxedandresiduesconsrved
in all selectins are shaded. This sequence-structurealignment
provided the basis for comparative model building of the
P-selectinligand-binding domain. B: Model structure of li-
gand-bindng domain of P-selectin. The model,represented as
a solid was ased on identified structural similar-
ity to crystal structure of the C-typelectindomain of the rat
mannose-bindingdomain, whichrevealed a previouslyunknown
roteinfold.The iewis longa-helix 2, locatedbelow theloop
regioncoloredinyellow. A conservedcalciumpositionisshwn
in red.Analyisof the modelsuggeste a shallowdepression
proximal to the conservedcalcium as a potentialligad-binding
ite.Thisregion is flankedn the left by loop, colored yel-
ow,with a five-residueinsertionreltive to the mannose-binding
Residues the roposedligand-bindingregion of
P-selectinweresubjected to ite-specificmutagenesisanalysis,
the hypothesisregarding the location ofrsidues in
P-selectincriticl inding to its cellularligand.Theresidues
are shown in a colorcoded ashion:magenta,crucialfor binding;
lavender,significant contribution to binding; blue, minorcon-
tribution to binding. C: Assessentof the P-selectinmodelby
comparison f 3D-profils of the MBPcrystal structure (rela-
tive to the MBPsequence)andoftheP-selectinmodelstructure
(relative to its sequence). The profiles were alculatedusing a
21-residuewindow for scoreaveraging. The calculatedZ-score
for the MBPsequence and crystal structure is30.8, the
Z-score for the P-selectinsequence and model is 34.9. No eg-
ative valueswereobserved that ould ocalin-
consistenciesin the structural odels. The analysissuggests n
equivalentcompatibiltyofsequenceandstructure he model
and the X-ray structure.
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