Improved sensitivity and resolution of in-cell NMR spectra

Methods Enzymol. 2019:621:305-328. doi: 10.1016/bs.mie.2019.02.029. Epub 2019 Mar 13.

Abstract

In-cell NMR spectroscopy is a powerful tool to study protein structures and interactions under near physiological conditions in both prokaryotic and eukaryotic living cells. The low sensitivity and resolution of in-cell NMR spectra and limited lifetime of cells over the course of an in-cell experiment have presented major hurdles to wide acceptance of the technique, limiting it to a few select systems. These issues are addressed by introducing the use of the CRINEPT pulse sequence to increase the sensitivity and resolution of in-cell NMR spectra and the use of a bioreactor to maintain cell viability for up to 24h. Application of advanced pulse sequences and bioreactor during in-cell NMR experiments will facilitate the exploration of a wide range of biological processes.

Keywords: Antibiotics; Atomic resolution structure; In vivo biochemistry; In-cell biochemistry; Nucleic acids; Protein interactions; Protein structure; Protein-drug interactions; RNA; Ribosome; Thioredoxin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bioreactors*
  • Cell Survival
  • Drug Evaluation, Preclinical / instrumentation
  • Drug Evaluation, Preclinical / methods
  • Equipment Design
  • Escherichia coli / chemistry
  • Escherichia coli / cytology
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • HeLa Cells
  • Humans
  • Microbial Viability
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular / instrumentation*
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Protein Interaction Mapping / methods
  • Proteins / chemistry*
  • Proteins / metabolism
  • Software

Substances

  • Escherichia coli Proteins
  • Proteins