Extending the Applicability of Exact Nuclear Overhauser Enhancements to Large Proteins and RNA

Parker J Nichols; Alexandra Born; Morkos A Henen; Dean Strotz; Chi N Celestine; Peter Güntert; Beat Vögeli

doi:10.1002/cbic.201800237

Extending the Applicability of Exact Nuclear Overhauser Enhancements to Large Proteins and RNA

Chembiochem. 2018 Jun 8. doi: 10.1002/cbic.201800237. Online ahead of print.

Authors

Parker J Nichols¹, Alexandra Born¹, Morkos A Henen^{1

2}, Dean Strotz³, Chi N Celestine⁴, Peter Güntert^{3

5

6}, Beat Vögeli¹

Affiliations

¹ Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO, 80045, USA.
² Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
³ Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.
⁴ Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, 75123, Uppsala, Sweden.
⁵ Institute of Biophysical Chemistry, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, 60438, Frankfurt am Main, Germany.
⁶ Graduate School of Science, Tokyo Metropolitan University, 1-1 Minami-ohsawa, Hachioji, Tokyo, 192-0397, Japan.

PMID: 29883016
DOI: 10.1002/cbic.201800237

Abstract

Distance-dependent nuclear Overhauser enhancements (NOEs) are one of the most popular and important experimental restraints for calculating NMR structures. Despite this, they are mostly employed as semiquantitative upper distance bounds, and this discards the wealth of information that is encoded in the cross-relaxation rate constant. Information that is lost includes exact distances between protons and dynamics that occur on the sub-millisecond timescale. Our recently introduced exact measurement of the NOE (eNOE) requires little additional experimental effort relative to other NMR observables. So far, we have used eNOEs to calculate multistate ensembles of proteins up to approximately 150 residues. Here, we briefly revisit eNOE methodology and present two new directions for the use of eNOEs: applications to large proteins and RNA.

Keywords: NMR spectroscopy; RNA; dynamics; nuclear Overhauser effect; proteasomes.

Publication types

Review