The overall objective of the research is to elucidate the structural and mechanistic characteristics of microsomal glutathione transferase, a membrane-bound enzyme involved in the catalytic addition of glutathione to toxic reaction intermediates. Very little is known about the structure and mechanism of microsomal GSH transferase (MGST1) other than a low-resolution three-dimensional protein map, which does not address activation of the enzyme and how the protein dynamics may change in response to ligands binding. The research to be undertaken will investigate the role of protein dynamics in the catalytic mechanism of MGSTI. The kinetics of backbone amide HID exchange is well-established as a sensitive indicator of protein structure and dynamics. Amide H/D exchange mass spectrometry (ESI-TOF) provides an amenable technique to study the dynamics of MGST1, with future application to other membrane proteins. The kinetic results should be a valuable tool of assessing the accuracy of the low resolution structure, as well as understanding specific segmental motions that may affect catalysis.