Abstract:
:GSTs catalyze the conjugation of glutathione with a wide variety of hydrophobic compounds, generally resulting in nontoxic products that can be readily eliminated. In contrast to many other organisms, the malarial parasite Plasmodium falciparum possesses only one GST isoenzyme (PfGST). This GST is highly abundant in the parasite, its activity was found to be increased in chloroquine-resistant cells, and it has been shown to act as a ligandin for parasitotoxic hemin. Thus, the enzyme represents a promising target for antimalarial drug development. We now have solved the crystal structure of PfGST at a resolution of 1.9 A. The homodimeric protein of 26 kDa per subunit represents a GST form that cannot be assigned to any of the known GST classes. In comparison to other GSTs, and, in particular, to the human isoforms, PfGST possesses a shorter C-terminal section resulting in a more solvent-accessible binding site for the hydrophobic and amphiphilic substrates. The structure furthermore reveals features in this region that could be exploited for the design of specific PfGST inhibitors.
journal_name
Proc Natl Acad Sci U S Aauthors
Fritz-Wolf K,Becker A,Rahlfs S,Harwaldt P,Schirmer RH,Kabsch W,Becker Kdoi
10.1073/pnas.2333763100keywords:
subject
Has Abstractpub_date
2003-11-25 00:00:00pages
13821-6issue
24eissn
0027-8424issn
1091-6490pii
2333763100journal_volume
100pub_type
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