Three-dimensional structure of the immunophilin-like domain of FKBP59 in solution.

FKBP59 is a protein usually associated with heat-shock protein hsp90 and steroid receptors. The N-terminal domain of the rabbit liver protein (149 amino acids) has a sequence homology with FKBP12, binds FK506 immunosuppressor, and has a peptidyl−prolyl cis−trans isomerase activity. The three-dimensional structure of this domain (FKBP59-I) was determined using homo- and heteronuclear multidimensional NMR spectroscopy, distance geometry, and molecular dynamics methods. Structure calculations used 1290 interproton distance restraints derived from nuclear Overhauser enhancement measurements, 29 dihedral φ angle restraints, and 92 hydrogen bond restraints. For the final 22 structures, the root mean square distance from the mean atomic coordinates, calculated for well-defined secondary structure fragments, is 0.47 ± 0.05 and 1.26 ± 0.15 A for backbone heavy atoms (N, Cα, C‘) and for all non-hydrogen atoms, respectively. The global fold contains a twisted six-stranded antiparallel β-sheet and a short α-helix pac...