5IJS

Crystal structure of autotaxin with orthovanadate bound as a trigonal bipyramidal intermediate analog

5IJS の概要

• エントリーDOI: 10.2210/pdb5ijs/pdb
• 関連するPDBエントリー: 5dlt 5ijq
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 7alpha-hydroxycholesterol, ... (8 entities in total)
• 機能のキーワード: hydrolase, lysophosphatidylcholine, somatomedin, inflammation, metastasis, neuropathic pain, vascular development, neural development
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 96956.95

構造登録者

Hausmann, J.,Joosten, R.P.,Perrakis, A. (登録日: 2016-03-02, 公開日: 2016-06-15, 最終更新日: 2025-07-30)

主引用文献

Hausmann, J.,Keune, W.J.,Hipgrave Ederveen, A.L.,van Zeijl, L.,Joosten, R.P.,Perrakis, A.
Structural snapshots of the catalytic cycle of the phosphodiesterase Autotaxin.
J.Struct.Biol., 195:199-206, 2016

PubMed Abstract: Autotaxin (ATX) is a secreted phosphodiesterase that produces the signalling lipid lysophosphatidic acid (LPA). The bimetallic active site of ATX is structurally related to the alkaline phosphatase superfamily. Here, we present a new crystal structure of ATX in complex with orthovanadate (ATX-VO5), which binds the Oγ nucleophile of Thr209 and adopts a trigonal bipyramidal conformation, following the nucleophile attack onto the substrate. We have now a portfolio of ATX structures we discuss as intermediates of the catalytic mechanism: the new ATX-VO5 structure; a unique structure where the nucleophile Thr209 is phosphorylated (ATX-pThr). Comparing these to a complex with the LPA product (ATX-LPA) and with a complex with a phosphate ion (ATX-PO4), that represent the Michaelis complex of the reaction, we observe movements of Thr209, changes in the relative displacement of the zinc ions, and a water molecule that likely fulfils the second nucleophilic attack. We propose that ATX follows the associative two-step in-line displacement mechanism.

PubMed: 27268273
DOI: 10.1016/j.jsb.2016.06.002

実験手法

X-RAY DIFFRACTION (2.2 Å)