Global and local motions in ribonuclease A: A
molecular dynamics study
Merlino A, Vitagliano L, Ceruso MA,
Di Nola A, Mazzarella L
BIOPOLYMERS
65 (4): 274-283 NOV
15 2002
Abstract:
The understanding of protein dynamics is one of the major goals of structural biology. A direct link between protein dynamics and function has been provided by x-ray, studies performed on ribonuclease A (RNase A) (B. F. Rasmussen et al., Nature, 1992, Vol. 357, pp. 423-424; L. Vitagliano et al., Proteins: Structure, Function, and Genetics, 2002, Vol. 46, pp. 97 104). Here we report a 3 its molecular dynamics simulation of RNase A in water aimed at characterizing the dynamical behavior of the enzyme. The analysis of local and global motions provides interesting insight on the dynamics/function relationship of RNase A. In agreement with previous crystallographic reports, the present study confirms that the RNase A active site is constituted by rigid (His12, Asn44, Thr45) and flexible (Lys41, Asp83, His119, Asp121) residues. The analysis of the global motions, performed using essential dynamics, shows that the two beta-sheet regions of RNase A move coherently in opposite directions, thus modifying solvent accessibility of the active site, and that the mixed alpha/3(10)-helix (residues 50-60) behaves as a mechanical hinge during the breathing motion of the protein. These data demonstrate that this motion, essential for RNase A substrate binding and release, is an intrinsic dynamical property of the ligand-free enzyme. (C) 2002 Wiley Periodicals, Inc.
Author Keywords:
ribonucleases, protein dynamics, protein structure-function, molecular dynamics, essential dynamics
KeyWords Plus:
BOVINE PANCREATIC RIBONUCLEASE, ASP CATALYTIC DYAD, MAGNETIC-RESONANCE SPECTROSCOPY, X-RAY STRUCTURE, RNASE-A, CRYSTAL-STRUCTURE, WILD-TYPE, SEMINAL RIBONUCLEASE, ISOASPARTYL RESIDUE, FOLDING PATHWAY
Addresses:
Mazzarella L, Univ Naples Federico II, Dipartimento
Chim, Via Cinthia, I-80125 Naples, Italy
Univ Naples Federico II,
Dipartimento Chim, I-80125 Naples, Italy
CNR, Ctr Studio
Biocristallog, I-80134 Naples, Italy