The NMR solution structure of the isolated Apo Pin1 WW domain (6-39) reveals
that it adopts a twisted three-stranded antiparallel beta-sheet conformation,
very similar to the structure exhibited by the crystal of this domain in the
context of the two domain Pin1 protein. While the B factors in the apo x-ray
crystal structure indicate that loop 1 and loop 2 are conformationally well
defined, the solution NMR data suggest that loop 1 is quite flexible, at least
in the absence of the ligand. The NMR chemical shift and nuclear Overhauser
effect pattern exhibited by the 6-39 Pin1 WW domain has proven to be diagnostic
for demonstrating that single site variants of this domain adopt a normally
folded structure. Knowledge of this type is critical before embarking on
time-consuming kinetic and thermodynamic studies required for a detailed
understanding of beta-sheet folding.
