Structural and stability characteristics of a monothiol glutaredoxin: glutaredoxin-like protein 1 from Plasmodium falciparum

Biochim Biophys Acta. 2008 Jun;1784(6):946-52. doi: 10.1016/j.bbapap.2008.03.012. Epub 2008 Apr 11.


Recently discovered monothiol glutaredoxins with CXXS-active site sequence share a common structural motif and biochemical mechanism of action and are involved in multiple cellular functions. Here we report first studies on the structural and stability characterization of a monothiol glutaredoxin, in particular--PfGLP1. Our results demonstrate that in the native conformation, the enzyme has a compact core structure with a relatively flexible N-terminal portion having an open configuration. Comparative functional studies with the full-length and N-terminal truncated protein demonstrate that the flexible N-terminal portion does not play any significant role in functional activity of the protein. In contrast to other Grxs, PfGLP1 does not contain a Fe-S cluster. The pH dependent studies demonstrate that the protein is resistant to alkaline pH but highly sensitive to acidic pH and undergoes significant unfolding between pH 4 and 5. However, acidic conditions also do not induce complete unfolding of the enzyme. The protein is stabilized with a conformational free energy of about 3.2+/-0.1 kcal mol(-1). The protein is a highly cooperative molecule as during denaturant-induced equilibrium unfolding a simultaneous unfolding of the protein without stabilization of any partially folded intermediate is observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Circular Dichroism
  • Glutaredoxins / chemistry*
  • Glutaredoxins / genetics
  • Glutaredoxins / metabolism
  • Molecular Sequence Data
  • Molecular Weight
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / genetics
  • Protein Binding
  • Protein Denaturation
  • Protons
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Temperature


  • Glutaredoxins
  • Protons
  • Protozoan Proteins