4ZXG

Ligandin binding site of PfGST

4ZXG の概要

• エントリーDOI: 10.2210/pdb4zxg/pdb
• 分子名称: Glutathione S-transferase, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: gst, plasmodium falciparum, hemin, transferase
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49259.50

構造登録者

Perbandt, M.,Eberle, R.,Betzel, C. (登録日: 2015-05-20, 公開日: 2015-06-24, 最終更新日: 2024-01-10)

主引用文献

Perbandt, M.,Eberle, R.,Fischer-Riepe, L.,Cang, H.,Liebau, E.,Betzel, C.
High resolution structures of Plasmodium falciparum GST complexes provide novel insights into the dimer-tetramer transition and a novel ligand-binding site.
J.Struct.Biol., 191:365-375, 2015

PubMed Abstract: Protection from oxidative stress and efficient redox regulation are essential for malarial parasites which have to grow and multiply rapidly in pro-oxidant rich environments. Therefore, redox active proteins currently belong to the most attractive antimalarial drug targets. The glutathione S-transferase from Plasmodium falciparum (PfGST) is a redox active protein displaying a peculiar dimer-tetramer transition that causes full enzyme-inactivation. This distinct structural feature is absent in mammalian GST isoenzyme counterparts. A flexible loop between residues 113-119 has been reported to be necessary for this tetramerization process. However, here we present structural data of a modified PfGST lacking loop 113-119 at 1.9 Å resolution. Our results clearly show that this loop is not essential for the formation of stable tetramers. Moreover we present for the first time the structures of both, the inactive and tetrameric state at 1.7 Å and the active dimeric state in complex with reduced glutathione at 2.4 Å resolution. Surprisingly, the structure of the inactive tetrameric state reveals a novel non-substrate binding-site occupied by a 2-(N-morpholino) ethane sulfonic acid (MES) molecule in each monomer. Although it is known that the PfGST has the ability to bind lipophilic anionic ligands, the location of the PfGST ligand-binding site remained unclear up to now.

PubMed: 26072058
DOI: 10.1016/j.jsb.2015.06.008

実験手法

X-RAY DIFFRACTION (1.7 Å)