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Figure 1.
Figure 1. (a) Sequence comparison of representative WW
domains. The sequences of the single WW of FE65, dystrophin, and
Pin1, the first WW of FBP11, PRP40, YAP65, and Nedd4, and the
second WW of FBP28, were aligned using the program CLUSTAL W.^56
Hyphens represent gaps inserted for optimum alignment. The
secondary structure elements of FE65 WW are indicated at the
top. Residues of human FE65 are numbered. Two conserved
tryptophan residues (after which the domain is named) are shown
in white on a blue background. Invariant tyrosine residues
(shown in white on a red background) and bulky hydrophobic
residues (highlighted in yellow) form the XP2 groove in group
II/III domains. Conserved threonine/serine residues that
hydrogen bond with the ligand are highlighted in green. (b)
Ribbon diagram of the FE65 WW domain. Residues that form the XP
and XP2 groves are shown as yellow stick models. The side-chains
of residues forming a hydrophobic core that stabilizes the fold
are shown in pink. (c) A stereo view of eight FE65 WW molecules
present in the asymmetric unit. Superposition of these
independent structures shows that they fall into two distinct
conformations highlighted in shades of green (apo form) and pink
(bound to a PEG400 molecule). Note the conformational changes of
the W271 and Y269 side-chains in the bound form. (d) In the apo
form, the XP2 groove is shallow. (e) Binding of a PEG400
molecule induces the formation of a deep XP2 groove, primarily
through conformational changes of the indole side-chain of W271
and, to a lesser degree, of the phenyl ring of Y269. The Figure
was made using PyMol [www.pymol.org].
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