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Figure 6.
Fig. 6. Variation in positioning of the region that lies
N-terminal to the inhibitor site: (a) Highlighted N-terminal
binding regions of PKI (dark teal), RIα (light green), and
RIIβ (red) demonstrate differential binding between inhibitors.
RIIβ and PKI dock to the C-lobe, while RIα docks to the
C-terminal tail and N-lobe. Surface mesh representation is shown
for the highly conserved P − 3 to P + 1 region. Details of
RIIβ binding peptide are highlighted. (b) The sequence and
detailed structural comparison of the inhibitor peptides of PKI,
RIα, and RIIβ. (c) The αF–αG loop (tan) creates a
hydrophobic pocket that recognizes different substrates (red).
Tyr235^C and Phe239^C are highly conserved residues in this
pocket. The region of RIIβ that lies N-terminally to the
inhibitor site docks as a strand to this pocket (left) while the
amphipathic helix of PKI (right) docks to the same surface. In
both cases, the peptides dock against Phe239^C. In
RIIβ(108–268), this site is unoccupied (middle) and the side
chain of Phe239^C is rotated away from Tyr235^C. In the two
RIIβ holoenzymes, one can see how Tyr247^C in the G-helix
interfaces with the P + 1 Val and with the Tyr226^R in the PBC
of RIIβ.
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