Abstract
Methionine residues within the kinase domain of Src serve as unique NMR probes capable of distinguishing between distinct conformational states of full-length Src, including alternative drug-inhibited forms. This approach offers a rapid method to differentiate between various inhibition mechanisms at any stage of drug development, eliminating the need to resolve the structure of Src-drug complexes. Using selectively (13)C-methyl-enriched methionine, spectra can be acquired in under an hour, while natural abundance spectra with comparable information are achievable within a few hours.