Structure determination of uniformly labelled ligands in receptor systems: Acetylcholine - A case study


Williamson, P.T.F., Verhoeven, A., Miller, K., Watts, A. and Meier, B. (2002) Structure determination of uniformly labelled ligands in receptor systems: Acetylcholine - A case study. Biophysical Journal, 82, (1), 518A-519A.

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Description/Abstract

Recent developments in SS-MAS-NMR methodology have brought about a wealth of information regarding the conformation and environment of small molecules bound to
membrane bound receptors. Currently the application of these methods to structure determination in biological systems has relied extensively on the ability to introduce isolated spin pairs and the subsequent determination of single internuclear distances using techniques such as rotational resonance or REDOR.
We present preliminary data on the application of rotational resonance experiments to the study of uniformly labelled molecules. Qualitatively the data obtained is similar to that
expected from systems labelled at unique sites. Analysis of such exchange curves obtained for a uniformly labelled acetylcholine perchlorate, using a model derived for
isolated spin pairs, shows good quantitative agreement between the observed geometries and those found in the crystal structure. Such experiments may offer an alternative to
selective labelling in some systems, reducing the time and expense associated with the preparation of multiple samples containing isolated spin pairs necessary for these studies
Progress is currently being made in the application of these techniques to the study of acetylcholine whilst bound to the nAcChR, with the aim of defining the global conformation of the molecule whilst bound to the receptor

Item Type: Article
ISSNs: 0006-3495 (print)
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 56138
Date Deposited: 07 Aug 2008
Last Modified: 27 Mar 2014 18:38
URI: http://eprints.soton.ac.uk/id/eprint/56138

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