Dynamic effects of mutations within two loops of
cytochrome c551 from Pseudomonas aeruginosa
Marc Antoine
Ceruso *, Alessandro Grottesi, Alfredo Di Nola
Proteins:
Structure, Function, and Genetics
Volume 50, Issue 2, 2003.
Pages: 222-229
Department of Chemistry, University of Rome La
Sapienza, Rome, Italy
email: Marc Antoine Ceruso
(mceruso@physbio.mssm.edu)
*Correspondence to Marc Antoine Ceruso, Department of Physiology and Biophysics, Mount Siani School of Medicine, One Gustave L. Levy Place, New York, NY 10029
Keywords
molecular dynamics • proline • glycine • protein function • protein stability
Abstract
In this work, we investigated the structural and dynamic consequences of two substitutions, P58A and G36P, located in two different solvent-exposed loops of cytochrome c551. The results show that both mutations affect regions that are distant from the site of mutation. Here, the two loops appear to be dynamically coupled to each other, because the substitution at one site affects the structure and the dynamics of the other site. However, the substitutions at Gly-36 and Pro-58 presented substantial differences, which were related to the mechanical (rigidity and deformability) properties of the site surrounding the mutation. Although the P58A mutant conserved a significant dynamic similarity to the wild-type protein as the immediate surroundings of position 58 became more rigid, the G36P mutant, which had deformed its flexible surroundings, presented a dynamic behavior that was markedly different from that of the wild-type protein. These results suggest that perturbation of sterically isolated and flexible regions, such as solvent-exposed loops, can have strong dynamic consequences on the protein as a whole, raising the possibility that these effects could in turn affect the stability or the function of the protein. Proteins