Enzyme-inhibitor complexes of lysozyme with glucosamine inhibitors. A molecular dynamics study through 2H-NMR.

2H relaxation measurements coupled with multiple specific 2H labeling have provided insight into the molecular dynamics of N-acetyl-D-glucosamine (GlcNAc) inhibitors bound to lysozyme. Deuteron T1 and T2 data for the bound state of methyl alpha- and -beta-GlcNAc 2H-labeled in the glycosidic methyl and C2 positions have been derived from measurements at different enzyme/inhibitor ratios. Rotational correlation times calculated therefrom for the labeled sites indicate, in both cases, tight binding for the sugar ring (tau(b) = 3.0 x 10(-9) s) accompanied by fast internal rotation, about one axis, of the glycosidic methyl groups (tau(r) = 5.5-7.6 x 10(-11) s). The small but consistent difference in the rates of internal rotation for the alpha- and beta-anomeric inhibitors may be indicative of different solution structures of the enzyme-inhibitor complexes.