STRUCTURAL DETERMINANTS OF PROTEIN DYNAMICS - ANALYSIS OF N-15 NMR RELAXATION MEASUREMENTS FOR MAIN-CHAIN AND SIDE-CHAIN NUCLEI OF HEN EGG-WHITE LYSOZYME

N-15-labeled hen lysozyme has been studied by 2D and 3D NMR in order t o characterize its dynamic behavior. The resonances of all main-chain amide nitrogen atoms were assigned, as were resonances of nitrogen ato ms in 28 side chains. Relaxation measurements for the main-chain and a rginine and tryptophan side-chain N-15 nuclei used standard methods, a nd those for the N-15 nuclei of asparagine and glutamine side chains u sed pulse sequences designed to remove unwanted relaxation pathways in the NH2 groups. The calculated order parameters (S-2) show that the m ajority of main-chain amides undergo only small amplitude librational motions on a fast time scale (S-2 greater than or equal to 0.8). Incre ased main-chain motion (0.5 < S-2 < 0.8) is observed for a total of 19 residues located at the C-terminus, in loop and turn regions, and in the first strand of the main beta-sheet. Order parameters derived for the side chains range from 0.05 to 0.9; five of the six tryptophan res idues have high order parameters (S-2 greater than or equal to 0.8), c onsistent with their location in the closely packed core of the protei n, whereas the order parameters between 0.05 and 0.3 for arginine resi dues confirm increased side-chain mobility at the protein surface. Ord er parameters for the side chains of asparagine and glutamine residues range from 0.2 to 0.8; high values are found for side chains that hav e low solvent accessible surfaces and well-defined chi(1) values, as m easured by (3)J(alpha beta) coupling constants. Many of the main-chain and side-chain groups with low order parameters have higher than aver age temperature factors in X-ray crystal structures and increased posi tional uncertainty in NMR solution structures. They also tend to lack persistent hydrogen bond interactions and protection against amide hyd rogen exchange. The most significant correlations are found between re sidues with low order parameters and high surface accessibility in bot h crystal and solution structures. The results suggest that a lack of van der Waals contacts is a major determinant of side-chain and main-c hain mobility in proteins.