NMR solution structure of the isolated Apo Pin1 WW domain: comparison to the x-ray crystal structures of Pin1.
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.
Kowalski
Jennifer A
JA
Department of Chemistry, Skaggs Institute of Chemical Biology, The Scripps Research Institute, BCC265 10550 N. Torrey Pines Road, La Jolla, CA 92037.
Liu
Kai
K
Kelly
Jeffery W
JW
D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012996:Solutions
D001051:Apoenzymes; D008024:Ligands; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012996:Solutions; D019696:Peptidylprolyl Isomerase