Dynamic structure of ribonuclease A in crystal and solution. Two major types of intramolecular motions

The conformatonal lability of residue side chains in ribonuclease A in crys tals and solution has been analyzed. Sixty one conformationally labile resi dues are identified in which side chains are displaced by >1 Angstrom in cr ystals of different space groups and/or are represented by pairs of alterna tive conformers in 11 crystal structures of RNase A. Polar and charged resi dues accessible to solvent predominate among them and are mostly found in l oop segments and in regions with distorted secondary structure, where steri c constraints of the conformational freedom of side chains are decreased du e to less tight packing. The population of the paired conformers is not enr iched in torsionally strained (about the chi(1) angle) side chain conformat ions. In solution (H-1-NMR data), the side chains of the majority of the co nformationally labile residues are dynamically disordered to varying extent and move nearly stochastically. Most residues involved in complex formatio n with RNase protein inhibitor are conformationally labile, and the rapidit y of their stochastic fluctuations allows for high rate of complex formatio n in solution. In the inner tightly packed regions, medium-scale fluctuatio ns important for crucial catalytic steps of covalent bond formation and bre akage, and large-scale fluctuations important for protein-protein interacti ons are observed along with small-amplitude vibrations.