Structural highlights
Function
[GST_PLAFA] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May also function as a storage protein or ligandin for parasitotoxic ferriprotoporphyrin IX (hemin).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The parasite Plasmodium falciparum causes malaria tropica, the most prevailing parasitic disease worldwide, with 300-500 million infections and 1.5-2.7 million deaths/year. The emergence of strains resistant to drugs used for prophylaxis and treatment and no vaccine available makes the structural analysis of potential drug targets essential. For that reason, we analyzed the three-dimensional structure of the glutathione S-transferase from P. falciparum (Pf-GST1) in the apoform and in complex with its inhibitor S-hexyl-glutathione. The structures have been analyzed to 2.6 and 2.2 A, respectively. Pf-GST1 shares several structural features with the Mu-type GSTs and is therefore closely related to this class, even though alignments with its members display low sequence identities in the range of 20-33%. Upon S-hexyl-glutathione binding, the overall structure and the glutathione-binding site (G-site) remain almost unchanged with the exception of the flexible C terminus. The detailed comparison of the parasitic enzyme with the human host Mu-class enzyme reveals that, although the overall structure is homologue, the shape of the hydrophobic binding pocket (H-site) differs substantially. In the human enzyme, it is shielded from one side by the large Mu-loop, whereas in Pf-GST1 the Mu-loop is truncated and the space to recognize and bind voluminous substrates is extended. This structural feature can be exploited to support the design of specific and parasite-selective inhibitors.
Native and inhibited structure of a Mu class-related glutathione S-transferase from Plasmodium falciparum.,Perbandt M, Burmeister C, Walter RD, Betzel C, Liebau E J Biol Chem. 2004 Jan 9;279(2):1336-42. Epub 2003 Sep 12. PMID:12972411[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Harwaldt P, Rahlfs S, Becker K. Glutathione S-transferase of the malarial parasite Plasmodium falciparum: characterization of a potential drug target. Biol Chem. 2002 May;383(5):821-30. PMID:12108547 doi:http://dx.doi.org/10.1515/BC.2002.086
- ↑ Liebau E, Bergmann B, Campbell AM, Teesdale-Spittle P, Brophy PM, Luersen K, Walter RD. The glutathione S-transferase from Plasmodium falciparum. Mol Biochem Parasitol. 2002 Sep-Oct;124(1-2):85-90. PMID:12387854
- ↑ Hiller N, Fritz-Wolf K, Deponte M, Wende W, Zimmermann H, Becker K. Plasmodium falciparum glutathione S-transferase--structural and mechanistic studies on ligand binding and enzyme inhibition. Protein Sci. 2006 Feb;15(2):281-9. Epub 2005 Dec 29. PMID:16385005 doi:10.1110/ps.051891106
- ↑ Perbandt M, Burmeister C, Walter RD, Betzel C, Liebau E. Native and inhibited structure of a Mu class-related glutathione S-transferase from Plasmodium falciparum. J Biol Chem. 2004 Jan 9;279(2):1336-42. Epub 2003 Sep 12. PMID:12972411 doi:http://dx.doi.org/10.1074/jbc.M309663200
