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Figure 1.
Fig. 1. Backbone substitution requirements for SH3 and WW
domain recognition. (A) Structural mapping of alanine and
sarcosine scanning results (Table 1). Peptide/domain complex
interfaces (8, 9) shown schematically. Ligands adopt a PPII
conformation, depicted schematically as a triangular prism.
Residue positions (spheres) are color-coded by class:
white--does not require either C^  - or
N-substitution (alanine and sarcosine tolerant); green--requires
C^ -substitution
(alanine tolerant, sarcosine intolerant); orange--requires
N-substitution (sarcosine tolerant, alanine intolerant). (B)
Minimally sufficient recognition unit for SH3 and WW domain
binding grooves. Schematic view of a single binding groove
cross-section, looking down the PPII helical axis (viewed from
left side of Fig. 1A). Minimally required atoms defined in this
study, a sequential pair of C^ - and
N-substituted residues, are solid black. The van der Waals
binding surface that these atoms present is shaded. (C) Distinct
mechanisms of proline recognition. Proline can be recognized by
a lock and key mechanism, utilizing the full chemical potential
of the side chain. In contrast, SH3 and WW domains recognized
key prolines based on N-substitution. This mechanism utilizes
relatively little of the binding potential of ligand or protein
(hatched surface) but is still highly discriminatory for proline
among natural amino acids.
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