Identification of solvent-exposed regions of an FK-506 analog, ascomycin, bound to FKBP using a paramagnetic probe

J Biomol NMR. 1992 Jan;2(1):11-8. doi: 10.1007/BF02192797.

Abstract

The solvent-exposed regions of (U-13C)ascomycin when bound to its putative target protein, FKBP, have been identified based on the different proton longitudinal relaxation rates (R1 = 1/T1) measured in the absence and presence of the paramagnetic relaxation reagent, 4-hydroxy-2,2,6,6-tetramethyl-piperidinyl-1-oxy (HyTEMPO). The proton T1S of bound ascomycin were determined using a pulse sequence (T1-HMQC) which consists of a 180 degree proton pulse and a variable delay (tau) followed by a heteronuclear multiple quantum correlation (HMQC) experiment. The solvent-exposed regions of ascomycin determined by these experiments are compared to NOE data in which ascomycin/FKBP contacts were identified and to the X-ray structure of the FK-506/FKBP complex.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carbon Isotopes
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cyclic N-Oxides
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Molecular Conformation
  • Protein Binding
  • Protein Conformation
  • Spin Labels
  • Tacrolimus / analogs & derivatives*
  • Tacrolimus / chemistry
  • Tacrolimus / metabolism*
  • Tacrolimus Binding Proteins
  • X-Ray Diffraction

Substances

  • Carbon Isotopes
  • Carrier Proteins
  • Cyclic N-Oxides
  • Spin Labels
  • immunomycin
  • Tacrolimus Binding Proteins
  • tempol
  • Tacrolimus