1TU8
STructure of Onchoverca volvulus Pi-class Glutathione S-transferase with its kompetitive inhibitor s-hexyl-GSH
Summary for 1TU8
| Entry DOI | 10.2210/pdb1tu8/pdb |
| Related | 1TU7 |
| Descriptor | Glutathione S-transferase 2, S-HEXYLGLUTATHIONE (3 entities in total) |
| Functional Keywords | transferase |
| Biological source | Onchocerca volvulus |
| Total number of polymer chains | 4 |
| Total formula weight | 98754.03 |
| Authors | Perbandt, M. (deposition date: 2004-06-24, release date: 2005-01-11, Last modification date: 2024-03-13) |
| Primary citation | Perbandt, M.,Hoppner, J.,Betzel, C.,Walter, R.D.,Liebau, E. Structure of the Major Cytosolic Glutathione S-Transferase from the Parasitic Nematode Onchocerca volvulus J.Biol.Chem., 280:12630-12636, 2005 Cited by PubMed Abstract: Onchocerciasis is a debilitating parasitic disease caused by the filarial worm Onchocerca volvulus. Similar to other helminth parasites, O. volvulus is capable of evading the host's immune responses by a variety of defense mechanisms, including the detoxification activities of the glutathione S-transferases (GSTs). Additionally, in response to drug treatment, helminth GSTs are highly up-regulated, making them tempting targets both for chemotherapy and for vaccine development. We analyzed the three-dimensional x-ray structure of the major cytosolic GST from O. volvulus (Ov-GST2) in complex with its natural substrate glutathione and its competitive inhibitor S-hexylglutathione at 1.5 and 1.8 angstrom resolution, respectively. From the perspective of the biochemical classification, the Ov-GST2 seems to be related to pi-class GSTs. However, in comparison to other pi-class GSTs, in particular to the host's counterpart, the Ov-GST2 reveals significant and unusual differences in the sequence and overall structure. Major differences can be found in helix alpha-2, an important region for substrate recognition. Moreover, the binding site for the electrophilic co-substrate is spatially increased and more solvent-accessible. These structural alterations are responsible for different substrate specificities and will form the basis of parasite-specific structure-based drug design investigations. PubMed: 15640152DOI: 10.1074/jbc.M413551200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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