title: Direct demonstration of structural similarity between native and denatured eglin C.
abstract: To characterize the long-range structure that persists in the unfolded form of the 70-residue protein eglin C, residual dipolar couplings (RDCs) for HN-N and HA-CA bond vectors were measured by NMR spectroscopy for both its low pH, urea denatured state and its native state. When the data sets for the two different structural states were compared, a statistically significant correlation was found, with both sets of dipolar couplings yielding a correlation coefficient of r = 0.47 to 0.51. This finding directly demonstrates that the denatured state of eglin C has a nativelike global structure, a conclusion reached indirectly for staphylococcal nuclease by combining two different types of NMR data. A simple computer simulation showed that the degree of variation in phi and psi angles that yields the RDC correlation of r = 0.5 was inversely dependent on the statistical segment length, ranging from +/-6 to +/-30 degrees at the upper limit. Stable nativelike topologies that persist on unfolding would explain the rapid refolding kinetics displayed by many proteins and might provide a natural barrier against amyloid fibril formation.
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lee
authors.forename: Marshall H
authors.initials: MH
authors.lastname: Edgell
authors.forename: David
authors.initials: D
authors.lastname: Shortle
mesh_terms: D000818:Animals; D003198:Computer Simulation; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins; D011994:Recombinant Proteins / Q000737:chemistry*; D015843:Serpins / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D014508:Urea
chemical_list: D011506:Proteins; D011994:Recombinant Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D014508:Urea