9316938, PI-Wagner: With the proteins flavodoxin and eglin c, basic aspects of protein mobility will be studied. The research will be based on xeteronuclear relaxation experiments of 15 N and 13 C and on homonuclear nuclear Overhauser effect (NOE) measurements. Fully 15 N or 13 C labeled proteins as well as 7 10% 13 C labeled proteins will be used for the studies. While conventional methods of studying protein structures yield static (rigid) models, this research focuses on the motions within the structural framework of biological macromolecules. The technology can be transferred to proteins that are targets for rational drug design. There it is generally important to know about the mobility vs. apparent rigidity of surface areas. Studies of side chain mobility may be particularly important for this aspect. ***Structure, mobility and structural disorder are important aspects of protein function, and protein target recognition. This will be studied with the ada protein, a DNA repair protein, a flavodoxin from Anacystis nidulans and the elastase inhibitor eglin c. The ada protein repai rs methylated DNA preventing transcription and replication artifacts. After demethylating DNA phosphate groups it undergoes a conformational change and becomes a transcriptional activator of its own gene. Thus the structure and mobility of free N terminal domains of ada, as well as complexes with DNA will be studied. Since the protein changes conformation while pursuing its function, studies of the mobility are expected to shed light on the mechanism of protein function.***
