3L7G

Crystal structure of organophosphate anhydrolase/prolidase

3L7G の概要

• エントリーDOI: 10.2210/pdb3l7g/pdb
• 関連するPDBエントリー: 3L24
• 分子名称: Xaa-Pro dipeptidase, N,N'-bis(1-methylethyl)phosphorodiamidic acid, MANGANESE (II) ION, ... (4 entities in total)
• 機能のキーワード: pita-bread, detoxification, dipeptidase, hydrolase, manganese, metal-binding, metalloprotease, protease
• 由来する生物種: Alteromonas sp.
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 178645.55

構造登録者

Vyas, N.K.,Nickitenko, A.,Quiocho, F.A. (登録日: 2009-12-28, 公開日: 2010-02-09, 最終更新日: 2023-09-06)

主引用文献

Vyas, N.K.,Nickitenko, A.,Rastogi, V.K.,Shah, S.S.,Quiocho, F.A.
Structural insights into the dual activities of the nerve agent degrading organophosphate anhydrolase/prolidase.
Biochemistry, 49:547-559, 2010

PubMed Abstract: The organophosphate acid anhydrolase (OPAA) is a member of a class of bimetalloenzymes that hydrolyze a variety of toxic acetylcholinesterase-inhibiting organophosphorus compounds, including fluorine-containing chemical nerve agents. It also belongs to a family of prolidases, with significant activity against various Xaa-Pro dipeptides. Here we report the X-ray structure determination of the native OPAA (58 kDa mass) from Alteromonas sp. strain JD6.5 and its cocrystal with the inhibitor mipafox [N,N'-diisopropyldiamidofluorophosphate (DDFP)], a close analogue of the nerve agent organophosphate substrate diisopropyl fluorophosphate (DFP). The OPAA structure is composed of two domains, amino and carboxy domains, with the latter exhibiting a "pita bread" architecture and harboring the active site with the binuclear Mn(2+) ions. The native OPAA structure revealed unexpectedly the presence of a well-defined nonproteinaceous density in the active site whose identity could not be definitively established but is suggestive of a bound glycolate, which is isosteric with a glycine (Xaa) product. All three glycolate oxygens coordinate the two Mn(2+) atoms. DDFP or more likely its hydrolysis product, N,N'-diisopropyldiamidophosphate (DDP), is present in the cocrystal structure and bound by coordinating the binuclear metals and forming hydrogen bonds and nonpolar interactions with active site residues. An unusual common feature of the binding of the two ligands is the involvement of only one oxygen atom of the glycolate carboxylate and the product DDP tetrahedral phosphate in bridging the two Mn(2+) ions. Both structures provide new understanding of ligand recognition and the prolidase and organophosphorus hydrolase catalytic activities of OPAA.

PubMed: 20000741
DOI: 10.1021/bi9011989

実験手法

X-RAY DIFFRACTION (2.7 Å)