NMR solution structure of the isolated Apo Pin1 WW domain: Comparison to the x‐ray crystal structures of Pin1

Abstract

The NMR solution structure of the isolated Apo Pin1 WW domain (6–39) reveals that it adopts a twisted three‐stranded antiparallel β‐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 β‐sheet folding. © 2002 John Wiley & Sons, Inc. Biopolymers 63: 111–121, 2002