1tu7
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(New page: 200px<br /><applet load="1tu7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tu7, resolution 1.50Å" /> '''Structure of Onchoce...)
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Revision as of 01:28, 21 November 2007
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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 with GTT and GOL as ligands. Active as Glutathione transferase, with EC number 2.5.1.18 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
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