HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 13, 12630-12636, April 1, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/13/12630    most recent M413551200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Perbandt, M. Articles by Liebau, E. Search for Related Content PubMed PubMed Citation Articles by Perbandt, M. Articles by Liebau, E. Social Bookmarking                      What's this?

Structure of the Major Cytosolic Glutathione S-Transferase from the Parasitic Nematode Onchocerca volvulus^*

Markus Perbandt, Jana Höppner¶, Christian Betzel, Rolf D. Walter¶, and Eva Liebau¶

From the Institute of Biochemistry and Foodchemistry, Department of Biochemistry and Molecularbiology, University of Hamburg, Martin Luther King Platz 6, 20146 Hamburg, Germany, and ^¶Department of Biochemistry, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany

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 Å resolution, respectively. From the perspective of the biochemical classification, the Ov-GST2 seems to be related to -class GSTs. However, in comparison to other -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 -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.

Received for publication, December 2, 2004

^* This work was supported by Deutscher Akademischer Austauschdienst (German Academic Exchange Service) Grant 415-probal/ale-03/17635. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and structure factors (codes 1TU7 and 1TU8) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

To whom correspondence should be addressed: Dept. of Biochemistry and Molecularbiology, Institute of Biochemistry and Foodchemistry, University of Hamburg, Martin Luther King Platz 6, 20146 Hamburg, Germany. Tel.: 49-40-89984745; Fax: 49-40-89984747; E-mail: Perbandt{at}chemie.uni-hamburg.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?