Enhancing the Sensitivity of CPMG Relaxation Dispersion to Conformational Exchange Processes by Multiple-Quantum Spectroscopy

Tairan Yuwen; Pramodh Vallurupalli; Lewis E Kay

doi:10.1002/anie.201605843

Enhancing the Sensitivity of CPMG Relaxation Dispersion to Conformational Exchange Processes by Multiple-Quantum Spectroscopy

Angew Chem Int Ed Engl. 2016 Sep 12;55(38):11490-4. doi: 10.1002/anie.201605843. Epub 2016 Aug 16.

Authors

Tairan Yuwen¹, Pramodh Vallurupalli², Lewis E Kay^{3

4}

Affiliations

¹ Departments of Molecular Genetics, Biochemistry and Chemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
² TIFR Centre for Interdisciplinary Sciences, 21 Brundavan Colony, Narsingi, Hyderabad, 500075, India.
³ Departments of Molecular Genetics, Biochemistry and Chemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. kay@pound.med.utoronto.ca.
⁴ Hospital for Sick Children, Program in Molecular Structure and Function, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada. kay@pound.med.utoronto.ca.

PMID: 27527986
DOI: 10.1002/anie.201605843

Abstract

A triple-quantum (1) H Carr-Purcell-Meiboom-Gill NMR relaxation dispersion experiment is presented that uses methyl group probes as reporters of conformational exchange in highly deuterated, methyl-protonated proteins. Significantly larger dispersion profiles, by as much as a factor of nine, can be obtained relative to single-quantum approaches, thus offering very significant advantages in applications involving interconverting conformers with only small changes in structure or in studies of rare states that are at very low populations. Applications to a number of protein systems are presented where the utility of the method, including its improved sensitivity to chemical exchange processes, is established.

Keywords: NMR spectroscopy; conformational dynamics; isotopic labeling; proteins.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

CIHR/Canada