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The native conformation of plasmepsin II is kinetically trapped at neutral pH. | LitMetric

The native conformation of plasmepsin II is kinetically trapped at neutral pH.

Arch Biochem Biophys

Department of Food Science, University of Guelph, Guelph, Ontario, Canada N1G2W1.

Published: September 2011

AI Article Synopsis

Article Abstract

Plasmepsin II (PMII), an aspartic protease from the malarial parasite Plasmodium falciparum, represents a model for understanding protease structure/function relationships due to its unique structure and properties. The present study undertook a thermodynamic and kinetic analysis of the PMII folding mechanism and a pH stability profile. Differential scanning calorimetry revealed that the native state of PMII (Np) was irreversibly unfolded, and in the pH range of 6.5-8.0, PMII refolds to a denatured state (Rp) with higher thermal stability than Np. Rp could also be formed upon partially unfolding PMII at pH 11.0 and 37 °C for 2h, followed by adjustment to a pH in the range of 6.5-8.0. While Rp could be folded/unfolded reversibly, Np was shown to exist as a kinetically trapped state. By examining the unfolding kinetics of Np and the kinetics of Rp folding to Np at 25 °C, it was found that Np is kinetically trapped by an unfolding barrier of 25.5 kcal/mol, and yet once unfolded, is prevented from folding by a comparable folding barrier. The folding mechanism of PMII is similar to that reported for pepsin. It is hypothesized that the PMII zymogen also utilizes a prosegment-catalyzed folding mechanism.

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Source
http://dx.doi.org/10.1016/j.abb.2011.06.017DOI Listing

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