NMR Studies of an FK-506 Analog, [U-13C]ascomycin, Bound to FK-506-binding Protein

A M Petros, G Gemmecker, P Neri, E T Olejniczak, D Nettesheim, R X Xu, E G Gubbins, H Smith, S W Fesik

J Med Chem. 1992 Jun 26;35(13):2467-73.

PMID: 1377749

Abstract:

Multidimensional, heteronuclear NMR methods were used to determine the complete 1H and 13C resonance assignments for [U-13C]ascomycin bound to recombinant FKBP, including stereospecific assignment of all 22 methylene protons. The conformation of ascomycin was then determined from an analysis of NOEs observed in a 13C-edited 3D HMQC-NOESY spectrum of the [U-13C]ascomycin/FKBP. This structure is found to be quite different from the solution structure of the two forms of uncomplexed FK-506. However, it is very similar to the X-ray crystal structure of FK-506 bound to FKBP, rms deviation = 0.56 A. The methods used for resonance assignment and structure calculation are presented in detail. Furthermore, FKBP/ascomycin NOEs are reported which help define the structure of the ascomycin binding pocket. This structural information obtained in solution was compared to the recently described X-ray crystal structure of the FKBP/FK-506 complex.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP104987124-A	Ascomycin solution		104987-12-4	Price