1YMN

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

1YMN の概要

• エントリーDOI: 10.2210/pdb1ymn/pdb
• 関連するPDBエントリー: 1YMR 1YMW
• 分子名称: Ribonuclease pancreatic (2 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Secreted: P61823
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13658.31

構造登録者

Xu, G.,Narayan, M.,Kurinov, I.,Ripoll, D.R.,Welker, E.,Khalili, M.,Ealick, S.E.,Scheraga, H.A. (登録日: 2005-01-21, 公開日: 2006-01-31, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.45 Å)