| he existence of multiple hexameric conformations of insulin has been well defined by x-ray crystallography. Insulin conformation within the hexamer has been shown to be dependent upon solution conditions, particularly, the presence of metal ions, protein concentration, pH and the presence of ligands, (Brange, 1987). Of particular interest is the induced structural change in residues Phe;Until recently NMR studies have been of limited value in probing the structure of the various insulin hexamers due to the aggregation affinity of the protein. The determination of conditions under which the monomeric unit can be maintained (Kline, 1990, Weiss, 1989) is a vital first step in this process. Although the hexameric unit is too large for the NMR experiment, a method has been developed by which the dynamics of the T;Efforts to produce an insulin mutant with decreased aggregation affinity and hence rapid pharmacologic activity have been moderately successful (Brange, 1988, 1990, Brems, 1992, Bryant, 1992). One such mutant was produced by transposing two amino acid residues in the B chain,... |
