5IJS: Crystal Structure Of Autotaxin With Orthovanadate Bound As A Trigonal Bipyramidal Intermediate Analog

Citation:
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 Ogamma 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.
PDB ID: 5IJSDownload
MMDB ID: 140121
PDB Deposition Date: 2016/3/2
Updated in MMDB: 2016/08
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 5IJS: monomeric; determined by software (PISA)
Molecular Components in 5IJS
Label Count Molecule
Protein (1 molecule)
1
Ectonucleotide Pyrophosphatase/phosphodiesterase Family Member 2(Gene symbol: Enpp2)
Molecule annotation
Chemicals (14 molecules)
1
2
2
1
3
2
4
1
5
6
6
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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