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Figure 3.
Fig. 3. Recognition of internal motifs by PDZ domains. In (A)
through (C), the GLGF loop acts as a steric block at the end of
the binding groove, necessitating chain termination or a sharp
 turn
immediately after the recognition motif. (A) Interaction
topology of a COOH-terminal peptide (orange) bound to PSD-95
PDZ3 (purple surface). (B) Interaction topology of the nNOS finger
(orange) with the syntrophin PDZ domain (purple surface). In (A)
and (B), the hydrophobic ligand residue that packs at site 0 is
shown in space-filling mode. Gray, carbon; red, oxygen. (C)
Schematic of structural requirements for PDZ domain recognition
of internal or COOH-terminal ligands. (D) Rigidly stabilized
structure of nNOS finger.
Overlay of C  traces of
the uncomplexed (orange) and complexed (grey) nNOS PDZ domain
structures, highlighting residues that stabilize the nNOS -finger
conformation. The main interaction is a salt bridge between
Arg^121 and Asp^62, which is buried by the surrounding
hydrophobic residues Ile^16, Leu^57, Pro^100, Phe^103, Thr^105,
Leu^107, and Thr^123. (E) Increased contact area in the PDZ
heterodimer through tertiary interactions. Solvent excluded
footprint of the nNOS PDZ domain (C trace
shown in orange) bound to the syntrophin PDZ domain (purple
surface, ~800 Å^2), compared to the footprint of a peptide
ligand (pink surface, ~400 Å^2). Images were generated
with the programs MOLSCRIPT (25) and WebLab Viewer Lite (26).
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