Biomedical Engineering Reference
In-Depth Information
CHAPTER 3
Making the Most of Chemical
Shifts
R. WILLIAM BROADHURST
Department of Biochemistry, 80 Tennis Court Road, University of
Cambridge, Cambridge CB2 1GA, UK
E-mail: rwb1002@cam.ac.uk
3.1 Introduction
The earliest high-resolution NMR studies of polypeptides and proteins
revealed that resonance frequencies are profoundly influenced by the local
environments created by secondary, tertiary and quaternary structure.
1,2
Although chemical shifts can be determined with high precision and provide
reliable markers of specific sites in protein structures, the relationship between
chemical shift and conformation proved difficult to unravel. Progress in this
area remained slow until cross-referenced databases of experimental structure
coordinates and frequency measurements became sufficiently large and
appropriate computational approaches were developed.
3-5
These innovations
now allow chemical shift data to report on a wide range of phenomena, from
local effects including post-translational modifications, backbone and side-
chain conformations, flexibility and solvent exposure; to global properties that
facilitate reference checking, assignment validation and three-dimensional
model building; and outwards to intermolecular interactions, by identifying
ligand binding surfaces and guiding the assembly of protein complexes.
This review focuses narrowly on the
1
H,
13
C and
15
N shifts commonly
studied
in
uniformly
labelled
protein
samples
and
their
applications
in
structural
biology
research.
For
brevity,
it
avoids
discussion
of
many
