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Slow Aromatic Ring Flips Detected Despite Near-Degenerate NMR Frequencies of the Exchanging Nuclei.

Weininger, Ulrich LU ; Respondek, Michal LU ; Löw, Christian and Akke, Mikael LU (2013) In The Journal of Physical Chemistry Part B 117(31). p.9241-9247
Abstract
Aromatic ring flips of Phe and Tyr residues are a hallmark of protein dynamics with a long history in molecular biophysics. Ring flips lead to symmetric exchange of nuclei between sites with distinct magnetic environments, which can be probed by NMR spectroscopy. Current knowledge of ring-flip rates originates from rare cases in which the chemical shift difference between the two sites is sufficiently large and the ring-flip rate sufficiently slow, typically kflip < 10(3) s(-1), so that separate peaks are observed in the NMR spectrum for the two nuclei, enabling direct measurement of the flip rate. By contrast, a great majority of aromatic rings show single peaks for each of the pairs of δ or ε nuclei, which commonly are taken as... (More)
Aromatic ring flips of Phe and Tyr residues are a hallmark of protein dynamics with a long history in molecular biophysics. Ring flips lead to symmetric exchange of nuclei between sites with distinct magnetic environments, which can be probed by NMR spectroscopy. Current knowledge of ring-flip rates originates from rare cases in which the chemical shift difference between the two sites is sufficiently large and the ring-flip rate sufficiently slow, typically kflip < 10(3) s(-1), so that separate peaks are observed in the NMR spectrum for the two nuclei, enabling direct measurement of the flip rate. By contrast, a great majority of aromatic rings show single peaks for each of the pairs of δ or ε nuclei, which commonly are taken as inferential evidence that the flip rate is fast, kflip ≫ 10(3) s(-1), even though rate measurements have not been achieved. Here we report a novel approach that makes it possible to identify slow ring flips in previously inaccessible cases where only single peaks are observed. We demonstrate that Y21 in the bovine pancreatic trypsin inhibitor (BPTI) has a slow ring-flip rate, kflip < 100 s(-1), a result that contrasts with previous estimates of 10(4)-10(6) s(-1) inferred from the single-peak spectrum of Y21. Comparison with a recent 1 ms molecular dynamics trajectory of BPTI shows qualitative agreement and highlights the value of accurate aromatic ring flip data as an important benchmark for molecular dynamics simulations of proteins across wide time scales. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
117
issue
31
pages
9241 - 9247
publisher
The American Chemical Society
external identifiers
  • wos:000323082200012
  • pmid:23859599
  • scopus:84881435079
ISSN
1520-5207
DOI
10.1021/jp4058065
language
English
LU publication?
yes
id
71aea534-0286-4ca4-8031-b13ee0493f50 (old id 3955866)
date added to LUP
2013-08-05 12:20:00
date last changed
2019-02-20 01:53:26
@article{71aea534-0286-4ca4-8031-b13ee0493f50,
  abstract     = {Aromatic ring flips of Phe and Tyr residues are a hallmark of protein dynamics with a long history in molecular biophysics. Ring flips lead to symmetric exchange of nuclei between sites with distinct magnetic environments, which can be probed by NMR spectroscopy. Current knowledge of ring-flip rates originates from rare cases in which the chemical shift difference between the two sites is sufficiently large and the ring-flip rate sufficiently slow, typically kflip &lt; 10(3) s(-1), so that separate peaks are observed in the NMR spectrum for the two nuclei, enabling direct measurement of the flip rate. By contrast, a great majority of aromatic rings show single peaks for each of the pairs of δ or ε nuclei, which commonly are taken as inferential evidence that the flip rate is fast, kflip ≫ 10(3) s(-1), even though rate measurements have not been achieved. Here we report a novel approach that makes it possible to identify slow ring flips in previously inaccessible cases where only single peaks are observed. We demonstrate that Y21 in the bovine pancreatic trypsin inhibitor (BPTI) has a slow ring-flip rate, kflip &lt; 100 s(-1), a result that contrasts with previous estimates of 10(4)-10(6) s(-1) inferred from the single-peak spectrum of Y21. Comparison with a recent 1 ms molecular dynamics trajectory of BPTI shows qualitative agreement and highlights the value of accurate aromatic ring flip data as an important benchmark for molecular dynamics simulations of proteins across wide time scales.},
  author       = {Weininger, Ulrich and Respondek, Michal and Löw, Christian and Akke, Mikael},
  issn         = {1520-5207},
  language     = {eng},
  number       = {31},
  pages        = {9241--9247},
  publisher    = {The American Chemical Society},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {Slow Aromatic Ring Flips Detected Despite Near-Degenerate NMR Frequencies of the Exchanging Nuclei.},
  url          = {http://dx.doi.org/10.1021/jp4058065},
  volume       = {117},
  year         = {2013},
}