Solid-state nuclear magnetic resonance structural studies of proteins using paramagnetic probes

Determination of three-dimensional structures of biological macromolecules by magic-angle spinning (MAS) solid-state NMR spectroscopy is hindered by the paucity of nuclear dipolar coupling-based restraints corresponding to distances exceeding 5 angstrom. Recent MAS NMR studies of uniformly C-13, N-15-enriched proteins containing paramagnetic centers have demonstrated the measurements of site-specific nuclear pseudocontact shifts and spin relaxation enhancements, which report on electron-nucleus distances up to similar to 20 angstrom. These studies pave the way for the application of such long-distance paramagnetic restraints to protein structure elucidation and analysis of protein-protein and protein-ligand interactions in the solid phase. Paramagnetic species also facilitate the rapid acquisition of high resolution and sensitivity multidimensional solid-state NMR spectra of biomacro-molecules using condensed data collection schemes, and characterization of solvent-accessible surfaces of peptides and proteins. In this review we discuss some of the latest applications of magic-angle spinning NMR spectroscopy in conjunction with paramagnetic probes to the structural studies of proteins in the solid state. (C) 2012 Elsevier Inc. All rights reserved.