Erythromycin A (EA) is a macrolide antibiotic that inhibits protein synthesis by binding to a bacterial ribosome. Actual structural infori-nation on the erythromycin-ribosome complex has been inaccessible due to the lack of available crystals and the poor resolution of the solution NMR spectra resulting from the slow reorientational motion of the ribosome. Consequently, the erythromycin-ribosome complex exhibits a solid-state NMR spectrum even in solution. The long-range objective of this collaboration is to determine the conformation of erythromycin A bound to a bacterial ribosome via solidstate NMR. Thus far, robust and efficient techniques for chemical shift correlation and multiple-quantum filtration via dipolar recoupling have been applied to uniformly """"""""C labeled erythromycin A. The twodimensional chemical shift correlation spectrum of U-""""""""C-erythromycin A, taken using the CMR7 double quantum mixing sequence, shows over 30 1-bond correlations and over 10 2-bond correlations. The increased resolution of the two-dimensional experiment allows the complete assignment of the """"""""C spectrum, the first step in structural determination. Detailed structural information will require multidimensional implementations of rotational resonance and torsion angle experiments, some of which are currently under development.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-23
Application #
6279702
Study Section
Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
23
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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