5IJS
Crystal structure of autotaxin with orthovanadate bound as a trigonal bipyramidal intermediate analog
Summary for 5IJS
| Entry DOI | 10.2210/pdb5ijs/pdb |
| Related | 5dlt 5ijq |
| Descriptor | 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) |
| Functional Keywords | hydrolase, lysophosphatidylcholine, somatomedin, inflammation, metastasis, neuropathic pain, vascular development, neural development |
| Biological source | Rattus norvegicus (Rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 96956.95 |
| Authors | Hausmann, J.,Joosten, R.P.,Perrakis, A. (deposition date: 2016-03-02, release date: 2016-06-15, Last modification date: 2024-01-10) |
| Primary citation | 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 Cited by 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: 27268273DOI: 10.1016/j.jsb.2016.06.002 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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