1tu7
From Proteopedia
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'''Structure of Onchocerca Volvulus Pi-class Glutathione S-transferase''' | '''Structure of Onchocerca Volvulus Pi-class Glutathione S-transferase''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Perbandt, M.]] | [[Category: Perbandt, M.]] | ||
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Revision as of 07:22, 3 May 2008
Structure of Onchocerca Volvulus Pi-class Glutathione S-transferase
Overview
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.
About this Structure
1TU7 is a Single protein structure of sequence from Onchocerca volvulus. Full crystallographic information is available from OCA.
Reference
Structure of the major cytosolic glutathione S-transferase from the parasitic nematode Onchocerca volvulus., Perbandt M, Hoppner J, Betzel C, Walter RD, Liebau E, J Biol Chem. 2005 Apr 1;280(13):12630-6. Epub 2005 Jan 7. PMID:15640152 Page seeded by OCA on Sat May 3 10:22:16 2008