5HRT

Crystal structure of mouse autotaxin in complex with a DNA aptamer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structural basis for specific inhibition of Autotaxin by a DNA aptamer

Kato, K.Ikeda, H.Miyakawa, S.Futakawa, S.Nonaka, Y.Fujiwara, M.Okudaira, S.Kano, K.Aoki, J.Morita, J.Ishitani, R.Nishimasu, H.Nakamura, Y.Nureki, O.

(2016) Nat Struct Mol Biol 23: 395-401

  • DOI: https://doi.org/10.1038/nsmb.3200
  • Primary Citation of Related Structures:  
    5HRT

  • PubMed Abstract: 

    ATX is a plasma lysophospholipase D that hydrolyzes lysophosphatidylcholine (LPC) and produces lysophosphatidic acid. To date, no ATX-inhibition-mediated treatment strategies for human diseases have been established. Here, we report anti-ATX DNA aptamers that inhibit ATX with high specificity and efficacy. We solved the crystal structure of ATX in complex with the anti-ATX aptamer RB011, at 2.0-Å resolution. RB011 binds in the vicinity of the active site through base-specific interactions, thus preventing the access of the choline moiety of LPC substrates. Using the structural information, we developed the modified anti-ATX DNA aptamer RB014, which exhibited in vivo efficacy in a bleomycin-induced pulmonary fibrosis mouse model. Our findings reveal the structural basis for the specific inhibition of ATX by the anti-ATX aptamer and highlight the therapeutic potential of anti-ATX aptamers for the treatment of human diseases, such as pulmonary fibrosis.


  • Organizational Affiliation

    Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2831Mus musculusMutation(s): 0 
Gene Names: Enpp2Npps2Pdnp2
EC: 3.1.4.39
UniProt
Find proteins for Q9R1E6 (Mus musculus)
Explore Q9R1E6 
Go to UniProtKB:  Q9R1E6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9R1E6
Sequence Annotations
Expand
  • Reference Sequence
Find similar nucleic acids by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains LengthOrganismImage
modified DNA (34-MER)34Homo sapiens
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
7N-Glycosylation
Glycosylation Resources
GlyTouCan:  G16404YH
GlyCosmos:  G16404YH
GlyGen:  G16404YH
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GOL
Query on GOL

Download Ideal Coordinates CCD File 
K [auth A]
L [auth A]
M [auth A]
N [auth A]
O [auth A]
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
G [auth A],
U [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
K
Query on K

Download Ideal Coordinates CCD File 
J [auth A]POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
I [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
H [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 120.062α = 90
b = 208.757β = 90
c = 90.036γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata processing
MOLREPphasing
Cootmodel building

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-04-06
    Type: Initial release
  • Version 1.1: 2016-05-25
    Changes: Database references
  • Version 1.2: 2020-02-19
    Changes: Data collection, Derived calculations
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary