NMR studies of an FK-506 analog, [U-13C]ascomycin, bound to FK-506-binding protein
| Autor: | Stephen W. Fesik, Andrew M. Petros, Harriet T. Smith, Placido Neri, Gerd Gemmecker, Earl G. Gubbins, David G. Nettesheim, Edward T. Olejniczak, Robert X. Xu |
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| Rok vydání: | 1992 |
| Předmět: |
Magnetic Resonance Spectroscopy
Stereochemistry T-Lymphocytes Gene Expression Crystal structure Tacrolimus Cell Line Tacrolimus Binding Proteins chemistry.chemical_compound X-Ray Diffraction Drug Discovery medicine Escherichia coli Molecule Humans Ascomycin Methylene Binding site Carbon Isotopes Chemistry Resonance (chemistry) Recombinant Proteins FKBP Heteronuclear molecule Genes Bacterial Molecular Medicine Carrier Proteins medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 35(13) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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