The results indicated that besides amino-acid residues Gln711, Arg752 and Thr877 which have previously been reported to be important in binding ligands, Leu701 and Leu704 are also important.
Possibly, the positively charged Arg and His residues near the aromatic Tyr residue proposed by Fantini to be important in binding via π-bonding interactions [1], actually attract SBD to more heavily sialylated gangliosides.
Conserved, solvent-exposed, Mpl-specific residues in the CD are likely to be instrumental in defining substrate specificity and include Arg357, Arg358, Phe374, Ala375, His376, His377, Glu402, Pro403, Arg404, Ser405, Asn406, Thr407, Ser483, Asn484 and Gly485, which may be important in binding tri, tetra, and pentapeptide substrates (Figure 9).
The third sequence rule mapped does not immediately correlate with any known residues important for binding but does contain two positively charged residues that may be important in binding, thus these residues may constitute a novel functional region.
The hairpin also introduces an Asp residue, which may be important in binding the free amino-terminal amino group of the substrate in the S2 binding site, in a manner reminiscent of other DPPs, such as DPP4.
The combination of an adaptable, promiscuous binding pocket with the strong anchoring recognition 20 for phosphothreonine, suggested that the combination may be important in binding a subset of PBD-interacting proteins, since to date there is little evidence to explain the diverse, yet highly regulated array of PBD-dependent Plk1 activities.
The 2′ and 4′ hydroxyl groups of the receiving Gal moiety are important in binding.
We have previously shown that c-CBL is important in binding CRKL and BCR/ABL in hematopoietic cells.
The TKB domain is important in binding to a number of molecules, and they then function in signal transduction.
This suggests that interactions between aromatic rings (π-π interactions) are important in binding to inactivated state.
ADAM2 has an ECD tripeptide in the disintegrin domain that was characterized by structure-function studies as important for ADAM2 binding to eggs [24], [25], and also has a sequence similar to the RX6DLPEF motif in ADAM15 that is important in binding ITGA9-ITGB1 [33] (RLAQDECDVTEY in mouse ADAM2, RPSFEECDLPEY in human ADAM2).
