Journal Article


Jens Erik Nielsen
Damien Farrell
Fergal O'Meara
John Bradley



physicochemical processes mutation molecular dynamics simulation mutagenesis site directed muramidase genetics chemistry hydrogen ion concentration animals protein denaturation hen egg lysozyme protein stability

Highly perturbed pKa values in the unfolded state of hen egg white lysozyme. (2011)

Abstract The majority of pK(a) values in protein unfolded states are close to the amino acid model pK(a) values, thus reflecting the weak intramolecular interactions present in the unfolded ensemble of most proteins. We have carried out thermal denaturation measurements on the WT and eight mutants of HEWL from pH 1.5 to pH 11.0 to examine the unfolded state pK(a) values and the pH dependence of protein stability for this enzyme. The availability of accurate pK(a) values for the folded state of HEWL and separate measurements of mutant-induced effects on the folded state pK(a) values, allows us to estimate the pK(a) values of seven acidic residues in the unfolded state of HEWL. Asp-48 and Asp-66 display pK(a) values of 2.9 and 3.1 in our analysis, thus representing the most depressed unfolded state pK(a) values observed to date. We observe a strong correlation between the folded state pK(a) values and the unfolded state pK(a) values of HEWL, thus suggesting that the unfolded state of HEWL possesses a large degree of native state characteristics.
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Full list of authors on original publication

Jens Erik Nielsen, Damien Farrell, Fergal O'Meara, John Bradley

Experts in our system

Jens Erik Nielsen
University College Dublin
Total Publications: 27
Damien Farrell
University College Dublin
Total Publications: 16