1TU7

Structure of Onchocerca Volvulus Pi-class Glutathione S-transferase

Summary for 1TU7

• Entry DOI: 10.2210/pdb1tu7/pdb
• Related: 1TU8
• Descriptor: Glutathione S-transferase 2, GLUTATHIONE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: transferase
• Biological source: Onchocerca volvulus
• Total number of polymer chains: 2
• Total formula weight: 49298.77

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

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: 15640152
DOI: 10.1074/jbc.M413551200

Experimental method

X-RAY DIFFRACTION (1.5 Å)