Solution structure of FK506 bound to FKBP-12

• Published in: FEBS letters Vol. 302; no. 1; pp. 89 - 96
• Main Authors: Lepre, Christopher A., Thomson, John A., Moore, Jonathan M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.05.1992; Elsevier
• Subjects: Biological and medical sciences; Carrier Proteins - chemistry; Carrier Proteins - metabolism; correlated spectroscopy; COSY; CsA; cyclophilin; cyclosporin A; CyP; distance geometry; double quantum; double quantum filtered; DQF; FK506; FK506 binding protein (11.8 kDa); FKBP; FKBP-12; GARP; globally optimized alternating-phase rectangular pulses; heteronuclear multiple quantum coherence spectroscopy; heteronuclear single quantum coherence spectroscopy; heteronuclear single quantum coherence-nuclear Overhauser enhancement spectroscopy; HMQC; hrFKBP-12; HSQC; HSQC-NOESY; human recombinant FKBP-12; Immunomodulators; Immunophilin; Magnetic Resonance Spectroscopy; Medical sciences; Models, Molecular; Molecular Conformation; molecular dynamics; Molecular Structure; NMR; NOE; NOESY; nuclear magnetic resonance; nuclear Overhauser enhancement; Peptidyl-prolyl cis-trans isomerase; Pharmacology. Drug treatments; Solutions; Tacrolimus - chemistry; Tacrolimus - metabolism; Tacrolimus Binding Proteins; TOCSY; total correlation spectroscopy; two dimensional; two-dimensional NOE spectroscopy; Peptidyl-prolyl cis-trans isomerase; DG; NOE; HSQC-NOESY; TOCSY; FK506; COSY; DQ; FKBP-12; CsA; NMR; 2D; FKBP; HMQC; MD; DQF; hrFKBP-12; GARP; NOESY; CyP; HSQC; Immunophilin; Signal transduction; Enzyme; Overhauser effect; NMR spectrometry; Method; Isomerase; Structural analysis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(92)80292-O

The complex of the immunosuppressant FK506 bound to FKBP-12 has been studied in solution using 1H and inverse-detected 13C NMR methods. The resonances of bound, 13C-labelled FK506 were assigned and a set of 66 intraligand NOE distance restraints were used to calculate the structure of the bound ligand by distance geometry and restrained molecular dynamics methods. The structure of bound FK506 in solution closely resembles that seen in the X-ray structure [17], except for the allyl region. The differences reflect the influence of intermolecular crystal contacts and have implications for interpretation of the interaction of the FK506/FKBP complex with its putative biological receptor.