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Figure 5.
Figure 5. Inhibitor 2 binding to PKA and PKB. (a) PKA-2 and
(b) PKB-2 (in the region of the ATP site). Final 2mF[o]–DF[c]
electron density for the inhibitors is contoured at 1σ and
shown in blue. (c) Superposition of PKA-2 (grey) and PKB-2
(yellow). Residues are labelled using PKB numbering. (d)
Schematic diagram showing binding of 2 to PKA and PKB. Key
non-covalent interactions are depicted as broken lines. The
alternative positions of the indole ring are shown by shading:
PKA (light grey) and PKB (black). (e) Surface representation of
PKB with compound 2 bound. The surface was coloured by
lipophilicity in AstexViewer^46 using the method described by
Gaillard et al.,^53 with red/pink representing the most
lipophilic regions, and blue/green the least lipophilic. The
putative methyl-aromatic interaction discussed in the text is
shown as a broken line. (f) Overlay of surfaces for PKA (grey)
and PKB (yellow) with compound 2 bound. The indole group of 2
packs with the side-chain of Met282, but would leave a cavity in
PKA due to the substitution by leucine at this point in the
active site.
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