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Updated: May 30, 2026

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
19:16

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

Published on: March 17, 2010

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

Huogen Xiao1, Derek Dee, Rickey Y Yada

  • 1Department of Food Science, University of Guelph, Guelph, Ontario, Canada N1G2W1.

Archives of Biochemistry and Biophysics
|July 20, 2011
PubMed

Insights

Plasmepsin II (PMII) from Plasmodium falciparum exists in a kinetically trapped native state. This malarial protease refolds to a more stable denatured state, revealing insights into protease folding mechanisms.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Parasitology

Background:

  • Plasmepsin II (PMII) is an aspartic protease from the malarial parasite Plasmodium falciparum.
  • PMII serves as a model for studying protease structure-function relationships due to its unique characteristics.

Purpose of the Study:

  • To investigate the thermodynamic and kinetic aspects of the PMII folding mechanism.
  • To determine the pH stability profile of PMII.

Main Methods:

  • Differential scanning calorimetry (DSC) was employed to analyze PMII's thermal stability and unfolding.
  • Kinetic studies examined the unfolding of the native state (Np) and the refolding of the denatured state (Rp).

Main Results:

  • The native state of PMII (Np) was found to be irreversibly unfolded.
  • PMII refolds to a more thermally stable denatured state (Rp) in the pH range of 6.5-8.0.
  • Rp exhibits reversible folding/unfolding, while Np is a kinetically trapped state with significant unfolding and folding barriers.

Conclusions:

  • PMII's native state is kinetically trapped, suggesting a complex folding pathway.
  • The folding mechanism of PMII shares similarities with pepsin.
  • It is hypothesized that the PMII zymogen employs a prosegment-catalyzed folding mechanism.

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