1ymn
The study of reductive unfolding pathways of RNase A (Y92L mutant)
OverviewOverview
Reductive unfolding studies of proteins are designed to provide information about intramolecular interactions that govern the formation (and stabilization) of the native state and about folding/unfolding pathways. By mutating Tyr92 to G, A, or L in the model protein, bovine pancreatic ribonuclease A, and through analysis of temperature factors and molecular dynamics simulations of the crystal structures of these mutants, it is demonstrated that the markedly different reductive unfolding rates and pathways of ribonuclease A and its structural homologue onconase can be attributed to a single, localized, ring-stacking interaction between Tyr92 and Pro93 in the bovine variant. The fortuitous location of this specific stabilizing interaction in a disulfide-bond-containing loop region of ribonuclease A results in the localized modulation of protein dynamics that, in turn, enhances the susceptibility of the disulfide bond to reduction leading to an alteration in the reductive unfolding behavior of the homologues. These results have important implications for folding studies involving topological determinants to obtain folding/unfolding rates and pathways, for protein structure-function prediction through fold recognition, and for predicting proteolytic cleavage sites.
About this StructureAbout this Structure
1YMN is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
A localized specific interaction alters the unfolding pathways of structural homologues., Xu G, Narayan M, Kurinov I, Ripoll DR, Welker E, Khalili M, Ealick SE, Scheraga HA, J Am Chem Soc. 2006 Feb 1;128(4):1204-13. PMID:16433537 Page seeded by OCA on Sat May 3 16:30:58 2008