1TU8

STructure of Onchoverca volvulus Pi-class Glutathione S-transferase with its kompetitive inhibitor s-hexyl-GSH

1TU8 の概要

• エントリーDOI: 10.2210/pdb1tu8/pdb
• 関連するPDBエントリー: 1TU7
• 分子名称: Glutathione S-transferase 2, S-HEXYLGLUTATHIONE (3 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Onchocerca volvulus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 98754.03

構造登録者

Perbandt, M. (登録日: 2004-06-24, 公開日: 2005-01-11, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)