David C. Dalgarno

Structural information from NMR secondary chemical shifts of peptide α C-H protons in proteins

The secondary chemical shift experienced by the1H-NMR resonances of the α C−H protons in proteins can be correlated with their backbone torsional angles ψ, which dictate the orientation of the α C−H proton to the adjacent carbonyl group. It is shown that α C−H protons present in β-sheet regions experience downfield secondary shifts , whereas those in α-helix regions experience upfield secondary shifts. The predictive use of this correlation in assignment studies is illustrated for the calcium-binding protein paravalbumin, for which a crystal structure is available, and troponin C, for which no crystallographic data are available.

The nature of the trifluoperazine binding sites on calmodulin and troponin-C.

We have employed 1H-nuclear magnetic resonance spectroscopy to study the interaction of the drug trifluoperazine with calmodulin and troponin-C. Distinct trifluoperazine-binding sites exist in the N- and C-terminal halves of both proteins. Each site consists of a group of hydrophobic side-chains brought into proximity by the Ca2+-dependent juxtaposition of two alpha-helical segments of the protein, each, in turn, belonging to a different Ca2+-binding site in the protein half. The trifluoperazine-induced inhibition of the biological activating ability of calmodulin appears to result from conformational restrictions conferred upon the protein by the bound drug.

The occurrence of α‐N‐trimethylalanine as the N‐terminal amino acid of some myosin light chains

The alkali light chains are small subunits of myosin; one is associated with each head region. Rabbit fast-twitch skeletal muscle myosin contains two types, A 1 (LC 1) and A2 (LC3), which occur in a ratio of 2: 1 [ 1,2]. These differ from one another primarily in that Al possesses a 41 residue N-terminal ‘tail’ rich in proline, lysine and alanine residues, although they are otherwise almost identical 131. ‘H-NMR spectrum of calmodulin 171. However, subsequent analyses confirmed that the unknown signal arises not from the heavy chain, but from the associated alkali light chain, A 1, which contains no trimethyllysine.

The calcium receptor and trigger

Abstract This review shows that research combining sequence and chemical knowledge, crystal structure studies and NMR examination of structure and dynamics in solution have been necessary to elucidate the workings of the calcium trigger. Now we know in essence the nature of this electrochemical-mechanical transduction device, we can speculate on the mode of operation of many other transmission devices in biology.