5IJS

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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Literature

Structural snapshots of the catalytic cycle of the phosphodiesterase Autotaxin.

Hausmann, J.Keune, W.J.Hipgrave Ederveen, A.L.van Zeijl, L.Joosten, R.P.Perrakis, A.

(2016) J Struct Biol 195: 199-206

  • DOI: https://doi.org/10.1016/j.jsb.2016.06.002
  • Primary Citation of Related Structures:  
    5IJQ, 5IJS

  • 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.


  • Organizational Affiliation

    Division of Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: jens.hausmann@mpi-muenster.mpg.de.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2827Rattus norvegicusMutation(s): 2 
Gene Names: Enpp2AtxNpps2
EC: 3.1.4.39 (PDB Primary Data), 3.1.4.4 (UniProt)
UniProt
Find proteins for Q64610 (Rattus norvegicus)
Explore Q64610 
Go to UniProtKB:  Q64610
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ64610
Glycosylation
Glycosylation Sites: 1Go to GlyGen: Q64610-1
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5JK
Query on 5JK

Download Ideal Coordinates CCD File 
C [auth A]7alpha-hydroxycholesterol
C27 H46 O2
OYXZMSRRJOYLLO-RVOWOUOISA-N
IOD
Query on IOD

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G [auth A]
H [auth A]
I [auth A]
J [auth A]
K [auth A]
IODIDE ION
I
XMBWDFGMSWQBCA-UHFFFAOYSA-M
ZN
Query on ZN

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D [auth A],
E [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

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F [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
NA
Query on NA

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M [auth A],
N [auth A]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
6BR
Query on 6BR
A
L-PEPTIDE LINKINGC4 H8 N O7 VThr
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.75α = 99.33
b = 63.45β = 105.91
c = 70.55γ = 99.51
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
Cootmodel building
PDB-REDOrefinement

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 5JKClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
KWFNetherlands--
NWONetherlands--
NWONetherlands723.013.003

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-15
    Type: Initial release
  • Version 1.1: 2016-06-22
    Changes: Database references
  • Version 1.2: 2016-07-13
    Changes: Database references
  • Version 2.0: 2019-04-24
    Changes: Data collection, Polymer sequence
  • Version 3.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Refinement description, Structure summary
  • Version 3.1: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary