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PDBsum entry 1ymw
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References listed in PDB file
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Key reference
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Title
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A localized specific interaction alters the unfolding pathways of structural homologues.
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Authors
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G.Xu,
M.Narayan,
I.Kurinov,
D.R.Ripoll,
E.Welker,
M.Khalili,
S.E.Ealick,
H.A.Scheraga.
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Ref.
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J Am Chem Soc, 2006,
128,
1204-1213.
[DOI no: ]
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PubMed id
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Abstract
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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.
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