NMR studies of an FK-506 analog, [U-13C]ascomycin, bound to FK-506-binding protein.
J Med Chem
; 35(13): 2467-73, 1992 Jun 26.
Article
in En
| MEDLINE
| ID: mdl-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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carrier Proteins
/
Tacrolimus
Limits:
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
1992
Document type:
Article