 protein dynamics on the micro- to millisecond time scale 
 is increasingly 
 found to be critical for biological function , as demonstrated by numerous 
 nmr relaxation dispersion studies . 
 methyl groups are excellent probes 
 of protein interactions and dynamics because of their favorable nmr 
 relaxation properties , which lead to sharp signals in the 1h and 13c nmr spectra . out of the six different methyl - bearing 
 amino acid residue types in proteins 
 , methionine plays a special role 
 because of its extensive side - chain flexibility and the high polarizability 
 of the sulfur atom . 
 methionine is over - represented in many protein  
 protein 
 recognition sites , making the methyl group of this residue type an 
 important probe of the relationships among dynamics , interactions , 
 and biological function . here 
 we present a straightforward method 
 to label methionine residues with specific 13chd2 methyl isotopomers against a deuterated background . 
 the resulting 
 protein samples yield nmr spectra with improved sensitivity due to 
 the essentially 100% population of the desired 13chd2 methyl isotopomer , which is ideal for 1h and 13c spin relaxation experiments to investigate protein dynamics 
 in general and conformational exchange in particular . 
 we demonstrate 
 the approach by measuring 1h and 13c cpmg relaxation 
 dispersion for the nine methionines in calcium - free calmodulin ( apo - cam ) . 
 
 the results show that the c - terminal domain , but not the n - terminal 
 domain , of apo - cam undergoes fast exchange between the ground state 
 and a high - energy state . 
 since target proteins are known to bind specifically 
 to the c - terminal domain of apo - cam , we speculate that the high - energy 
 state might be involved in target binding through conformational selection . 
Supplementary Material