1YMN

The study of reductive unfolding pathways of RNase A (Y92L mutant)

Summary for 1YMN

• Entry DOI: 10.2210/pdb1ymn/pdb
• Related: 1YMR 1YMW
• Descriptor: Ribonuclease pancreatic (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted: P61823
• Total number of polymer chains: 1
• Total formula weight: 13658.31

Authors

Xu, G.,Narayan, M.,Kurinov, I.,Ripoll, D.R.,Welker, E.,Khalili, M.,Ealick, S.E.,Scheraga, H.A. (deposition date: 2005-01-21, release date: 2006-01-31, Last modification date: 2024-11-06)

Primary citation

Xu, G.,Narayan, M.,Kurinov, I.,Ripoll, D.R.,Welker, E.,Khalili, M.,Ealick, S.E.,Scheraga, H.A.
A localized specific interaction alters the unfolding pathways of structural homologues.
J.Am.Chem.Soc., 128:1204-1213, 2006

PubMed Abstract: 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.

PubMed: 16433537
DOI: 10.1021/ja055313e

Experimental method

X-RAY DIFFRACTION (1.45 Å)