| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
* Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Italy; Dipartimento di Chimica, Università degli Studi di Napoli "Federico II," Naples, Italy; Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Naples, Italy; and Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York
Correspondence: Address reprint requests to Lelio Mazzarella, Dipartimento di Chimica, Università degli Studi di Napoli "Federico II," Complesso Universitario di Monte Sant'Angelo, Via Cynthia, 80125 Napoli, Italy. Tel.: 39-081674279; Fax: 39-081674090; E-mail: mazzarella{at}chemistry.unina.it.
Bovine pancreatic ribonuclease (RNase A) forms two 3-dimensional domain-swapped dimers with different quaternary structures. One dimer is characterized by the swapping of the C-terminal region (C-Dimer) and presents a rather loose structure. The other dimer (N-Dimer) exhibits a very compact structure with exchange of the N-terminal helix. Here we report the results of a molecular dynamics/essential dynamics (MD/ED) study carried out on the N-Dimer. This investigation, which represents the first MD/ED analysis on a three-dimensional domain-swapped enzyme, provides information on the dynamic properties of the active site residues as well as on the global motions of the dimer subunits. In particular, the analysis of the flexibility of the active site residues agrees well with recent crystallographic and site-directed mutagenesis studies on monomeric RNase A, thus indicating that domain swapping does not affect the dynamics of the active sites. A slight but significant rearrangement of N-Dimer quaternary structure, favored by the formation of additional hydrogen bonds at subunit interface, has been observed during the MD simulation. The analysis of collective movements reveals that each subunit of the dimer retains the functional breathing motion observed for RNase A. Interestingly, the breathing motion of the two subunits is dynamically coupled, as they open and close in phase. These correlated motions indicate the presence of active site intercommunications in this dimer. On these bases, we propose a speculative mechanism that may explain negative cooperativity in systems preserving structural symmetry during the allosteric transitions.
This article has been cited by other articles:
 |
|
 |
|
  A. Merlino, L. Mazzarella, A. Carannante, A. D. Fiore, A. D. Donato, E. Notomista, and F. Sica The Importance of Dynamic Effects on the Enzyme Activity: X-RAY STRUCTURE AND MOLECULAR DYNAMICS OF ONCONASE MUTANTS J. Biol. Chem., May 6, 2005; 280(18): 17953 - 17960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Merlino, M. A. Ceruso, L. Vitagliano, and L. Mazzarella Open Interface and Large Quaternary Structure Movements in 3D Domain Swapped Proteins: Insights from Molecular Dynamics Simulations of the C-Terminal Swapped Dimer of Ribonuclease A Biophys. J., March 1, 2005; 88(3): 2003 - 2012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gotte and M. Libonati Oligomerization of Ribonuclease A: TWO NOVEL THREE-DIMENSIONAL DOMAIN-SWAPPED TETRAMERS J. Biol. Chem., August 27, 2004; 279(35): 36670 - 36679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Sica, A. Di Fiore, A. Merlino, and L. Mazzarella Structure and Stability of the Non-covalent Swapped Dimer of Bovine Seminal Ribonuclease: AN ENZYME TAILORED TO EVADE RIBONUCLEASE PROTEIN INHIBITOR J. Biol. Chem., August 27, 2004; 279(35): 36753 - 36760. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
