Journal of Biomolecular NMR

, Volume 2, Issue 1, pp 11–18

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

  • Andrew M. Petros
  • Placido Neri
  • Stephen W. Fesik
Research Papers

DOI: 10.1007/BF02192797

Cite this article as:
Petros, A.M., Neri, P. & Fesik, S.W. J Biomol NMR (1992) 2: 11. doi:10.1007/BF02192797

Summary

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-I-oxy (HyTEMPO). The proton T1s of bound ascomycin were determined using a pulse sequence (T1-HMQC) which consists of a 180° proton pulse and a variable delay (τ) 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.

Keywords

FKBPAscomycinParamagnetic relaxationSolvent-exposed regions of bound ligandsT1

Copyright information

© ESCOM Science Publishers B.V. 1992

Authors and Affiliations

  • Andrew M. Petros
    • 1
  • Placido Neri
    • 1
  • Stephen W. Fesik
    • 1
  1. 1.Pharmaceutical Discovery DivisionAbbott LaboratoriesAbbott ParkUSA