High‐Resolution NMR of Folded Proteins in Hyperpolarized Physiological Solvents. Issue 51 (17th August 2018)

• Record Type: Journal Article
• Authors: Kadeřávek, Pavel; Ferrage, Fabien; Bodenhausen, Geoffrey; Kurzbach, Dennis
• Is Part Of: Chemistry. Volume 24:Issue 51(2018)
• Page Start: 13418
• Page End: 13423
• Publication Date: 2018-08-17
• Subjects: dissolution DNP -- hyperpolarized water -- cross-relaxation effect -- protein NMR spectroscopy -- proton exchange; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201802885
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Hyperpolarized 2D exchange spectroscopy (HYPEX) to obtain high‐resolution nuclear magnetic resonance (NMR) spectra of folded proteins under near‐physiological conditions is reported. The technique is based on hyperpolarized water, which is prepared by dissolution dynamic nuclear polarization and mixed in situ in an NMR spectrometer with a protein in a physiological saline buffer at body temperature. Rapid exchange of labile protons with the hyperpolarized solvent, combined with cross‐relaxation effects (NOEs), leads to boosted signal intensities for many amide 1 H– 15 N correlations in the protein ubiquitin. As the introduction of hyperpolarization to the target protein is mediated via the solvent, the method is applicable to a broad spectrum of target molecules. Abstract : NMR of proteins under physiological conditions suffers from weak signal intensities. Hyperpolarization exchange spectroscopy overcomes this limitation by selectively enhancing residue‐resolved NMR spectra of globular proteins by up to two orders of magnitude. The selective nature of the enhancements reflects the solvent interface of the target protein.