New methods have been developed which enhance the sensitivity of protein NMR by transferring magnetization from the H2O solvent to the protein. Pulsed field gradients and selective pulses are used to ensure that the water magnetization remains close to its equilibrium value during the entire experiment. Cross relaxation and exchange of labile protein protons with solvent then result in increased protein signal intensity. The enhancement ranges from 10-50% for most experiments that are conducted in H2O solution, to a three-fold enhancement when studying the interaction between solvent and protein. This new methodology was used to prove that the HIV protease inhibitor DMP-323 indeed displaces the conserved water molecule observed in other complexes between inhibitors and the protease.

Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Lee, Jung Ho; Ying, Jinfa; Bax, Ad (2016) Quantitative evaluation of positive ? angle propensity in flexible regions of proteins from three-bond J couplings. Phys Chem Chem Phys 18:5759-70
Vogeli, Beat; Yao, Lishan; Bax, Ad (2008) Protein backbone motions viewed by intraresidue and sequential HN-Halpha residual dipolar couplings. J Biomol NMR 41:17-28
Chill, Jordan H; Louis, John M; Delaglio, Frank et al. (2007) Local and global structure of the monomeric subunit of the potassium channel KcsA probed by NMR. Biochim Biophys Acta 1768:3260-70
Ying, Jinfa; Chill, Jordan H; Louis, John M et al. (2007) Mixed-time parallel evolution in multiple quantum NMR experiments: sensitivity and resolution enhancement in heteronuclear NMR. J Biomol NMR 37:195-204
Grishaev, Alexander; Ying, Jinfa; Bax, Ad (2006) Pseudo-CSA restraints for NMR refinement of nucleic acid structure. J Am Chem Soc 128:10010-1
Ying, Jinfa; Grishaev, Alexander; Bryce, David L et al. (2006) Chemical shift tensors of protonated base carbons in helical RNA and DNA from NMR relaxation and liquid crystal measurements. J Am Chem Soc 128:11443-54
Ying, Jinfa; Bax, Ad (2006) 2'-hydroxyl proton positions in helical RNA from simultaneously measured heteronuclear scalar couplings and NOEs. J Am Chem Soc 128:8372-3
Chill, Jordan H; Louis, John M; Miller, Christopher et al. (2006) NMR study of the tetrameric KcsA potassium channel in detergent micelles. Protein Sci 15:684-98
Ying, Jinfa; Grishaev, Alexander; Bax, Ad (2006) Carbon-13 chemical shift anisotropy in DNA bases from field dependence of solution NMR relaxation rates. Magn Reson Chem 44:302-10
Dam, Julie; Baber, James; Grishaev, Alexander et al. (2006) Variable dimerization of the Ly49A natural killer cell receptor results in differential engagement of its MHC class I ligand. J Mol Biol 362:102-13

Showing the most recent 10 out of 67 publications