[English] 日本語
Yorodumi
- PDB-8c7r: Crystal structure of rat autotaxin and compound MEY-003 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8c7r
TitleCrystal structure of rat autotaxin and compound MEY-003
ComponentsEctonucleotide pyrophosphatase/phosphodiesterase family member 2
KeywordsHYDROLASE / Inhibitor / co-crystal / ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)
Function / homology
Function and homology information


response to polycyclic arene / alkylglycerophosphoethanolamine phosphodiesterase / sphingolipid catabolic process / phospholipid catabolic process / phosphatidylcholine catabolic process / lysophospholipase activity / positive regulation of lamellipodium morphogenesis / phosphodiesterase I activity / scavenger receptor activity / alkylglycerophosphoethanolamine phosphodiesterase activity ...response to polycyclic arene / alkylglycerophosphoethanolamine phosphodiesterase / sphingolipid catabolic process / phospholipid catabolic process / phosphatidylcholine catabolic process / lysophospholipase activity / positive regulation of lamellipodium morphogenesis / phosphodiesterase I activity / scavenger receptor activity / alkylglycerophosphoethanolamine phosphodiesterase activity / polysaccharide binding / positive regulation of oligodendrocyte differentiation / negative regulation of cell-matrix adhesion / positive regulation of epithelial cell migration / positive regulation of focal adhesion assembly / estrous cycle / phospholipid metabolic process / positive regulation of substrate adhesion-dependent cell spreading / regulation of cell migration / cellular response to cadmium ion / cell chemotaxis / cellular response to estradiol stimulus / positive regulation of peptidyl-tyrosine phosphorylation / nucleic acid binding / immune response / calcium ion binding / positive regulation of cell population proliferation / extracellular space / zinc ion binding
Similarity search - Function
Somatomedin B domain, chordata / Somatomedin B -like domains / Somatomedin B domain / Somatomedin B-like domain superfamily / Somatomedin B domain / Somatomedin B domain (SMB) signature. / Somatomedin B (SMB) domain profile. / Type I phosphodiesterase/nucleotide pyrophosphatase/phosphate transferase / Type I phosphodiesterase / nucleotide pyrophosphatase / Extracellular Endonuclease, subunit A ...Somatomedin B domain, chordata / Somatomedin B -like domains / Somatomedin B domain / Somatomedin B-like domain superfamily / Somatomedin B domain / Somatomedin B domain (SMB) signature. / Somatomedin B (SMB) domain profile. / Type I phosphodiesterase/nucleotide pyrophosphatase/phosphate transferase / Type I phosphodiesterase / nucleotide pyrophosphatase / Extracellular Endonuclease, subunit A / DNA/RNA non-specific endonuclease / DNA/RNA non-specific endonuclease / DNA/RNA non-specific endonuclease / DNA/RNA non-specific endonuclease / DNA/RNA non-specific endonuclease superfamily / His-Me finger superfamily / Alkaline-phosphatase-like, core domain superfamily
Similarity search - Domain/homology
7alpha-hydroxycholesterol / IODIDE ION / Chem-T8R / Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.53 Å
AuthorsEymery, M.C. / McCarthy, A.A.
Funding supportEuropean Union, 1items
OrganizationGrant numberCountry
European Molecular Biology Organization (EMBO)European Union
Citation
Journal: Eur.J.Med.Chem. / Year: 2023
Title: Discovery of potent chromone-based autotaxin inhibitors inspired by cannabinoids.
Authors: Eymery, M.C. / Nguyen, K.A. / Basu, S. / Hausmann, J. / Tran-Nguyen, V.K. / Seidel, H.P. / Gutierrez, L. / Boumendjel, A. / McCarthy, A.A.
#1: Journal: Acta Crystallogr D Biol Crystallogr / Year: 2012
Title: Towards automated crystallographic structure refinement with phenix.refine.
Authors: Afonine, P.V. / Grosse-Kunstleve, R.W. / Echols, N. / Headd, J.J. / Moriarty, N.W. / Mustyakimov, M. / Terwilliger, T.C. / Urzhumtsev, A. / Zwart, P.H. / Adams, P.D.
#2: Journal: Acta Crystallogr D Struct Biol / Year: 2019
Title: Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix.
Authors: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty ...Authors: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty / Robert D Oeffner / Billy K Poon / Michael G Prisant / Randy J Read / Jane S Richardson / David C Richardson / Massimo D Sammito / Oleg V Sobolev / Duncan H Stockwell / Thomas C Terwilliger / Alexandre G Urzhumtsev / Lizbeth L Videau / Christopher J Williams / Paul D Adams /
Abstract: Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological ...Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological processes and to develop new therapeutics against diseases. The overall structure-solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data-quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time-consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command-line features of Phenix and streamlines the transition between programs, project tracking and re-running of previous tasks.
History
DepositionJan 17, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 22, 2023Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)100,73512
Polymers98,8261
Non-polymers1,90911
Water1,69394
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1450 Å2
ΔGint-64 kcal/mol
Surface area31830 Å2
MethodPISA
Unit cell
Length a, b, c (Å)53.529, 61.843, 63.850
Angle α, β, γ (deg.)104.010, 98.430, 93.270
Int Tables number1
Space group name H-MP1
Space group name HallP1
Symmetry operation#1: x,y,z

-
Components

-
Protein / Sugars , 2 types, 2 molecules A

#1: Protein Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 / E-NPP 2 / Autotaxin / Extracellular lysophospholipase D / LysoPLD


Mass: 98826.250 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Enpp2, Atx, Npps2 / Production host: Homo sapiens (human)
References: UniProt: Q64610, alkylglycerophosphoethanolamine phosphodiesterase
#2: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE

-
Non-polymers , 6 types, 104 molecules

#3: Chemical ChemComp-T8R / 5,7-bis(oxidanyl)-2-(1-pentylindol-3-yl)chromen-4-one


Mass: 363.406 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H21NO4 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-5JK / 7alpha-hydroxycholesterol / (3beta,7alpha,9beta,14beta)-cholest-5-ene-3,7-diol / 7α-Hydroxycholesterol


Mass: 402.653 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H46O2
#5: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#6: Chemical
ChemComp-IOD / IODIDE ION / Iodide


Mass: 126.904 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: I
#7: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Ca
#8: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 94 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.04 Å3/Da / Density % sol: 39.8 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 18-22% (m/v) PEG3350, 0.1-0.3 M NH4I and 0.1-0.3 M NaSCN

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.97625 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 20, 2021
Details: Be 1D CRL (vertical) and Rh Elliptical mirror (horizontal) focusing
RadiationMonochromator: Si111 channel cut mono / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 2.53→43.64 Å / Num. obs: 25651 / % possible obs: 98.2 % / Redundancy: 3.4 % / Biso Wilson estimate: 36.73 Å2 / CC1/2: 0.993 / Net I/σ(I): 6.7
Reflection shellResolution: 2.53→2.573 Å / Num. unique obs: 1302 / CC1/2: 0.852

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
XDSVERSION Feb 5, 2021 BUILT=20210323data reduction
AimlessVersion 0.7.7data scaling
PHASERversion 2.1.2phasing
autoPROC1.1.7 (20210420)data processing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.53→43.64 Å / SU ML: 0.3125 / Cross valid method: FREE R-VALUE / σ(F): 2.01 / Phase error: 26.8084
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2538 2004 7.81 %
Rwork0.2049 23644 -
obs0.2088 25648 98.2 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 44.14 Å2
Refinement stepCycle: LAST / Resolution: 2.53→43.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6262 0 92 94 6448
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00686530
X-RAY DIFFRACTIONf_angle_d0.90728867
X-RAY DIFFRACTIONf_chiral_restr0.0505934
X-RAY DIFFRACTIONf_plane_restr0.011144
X-RAY DIFFRACTIONf_dihedral_angle_d6.8819890
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.53-2.590.30641530.26151672X-RAY DIFFRACTION97.96
2.59-2.660.34261380.24121700X-RAY DIFFRACTION97.56
2.66-2.740.29271410.24181663X-RAY DIFFRACTION97.78
2.74-2.830.30331470.23751698X-RAY DIFFRACTION98.3
2.83-2.930.31471440.23571671X-RAY DIFFRACTION98.37
2.93-3.050.31371390.2421692X-RAY DIFFRACTION98.28
3.05-3.190.3181430.25091716X-RAY DIFFRACTION98.26
3.19-3.360.28571440.22881706X-RAY DIFFRACTION98.93
3.36-3.570.22061400.21441660X-RAY DIFFRACTION96.93
3.57-3.840.28131440.18811706X-RAY DIFFRACTION98.93
3.84-4.230.21751430.17691692X-RAY DIFFRACTION98.76
4.23-4.840.19581400.16321711X-RAY DIFFRACTION98.88
4.84-6.090.20471440.18931668X-RAY DIFFRACTION97.73
6.09-43.640.2251440.18481689X-RAY DIFFRACTION98.07
Refinement TLS params.Method: refined / Origin x: 22.1388886984 Å / Origin y: 14.4483001578 Å / Origin z: -9.62965685416 Å
111213212223313233
T0.105322859899 Å2-0.00955223792139 Å20.0294905116473 Å2-0.103846432535 Å20.00267100919534 Å2--0.114710155091 Å2
L0.515275957472 °20.0718618300792 °20.23906793229 °2-0.391733482538 °20.0790297615321 °2--0.551897839112 °2
S-0.00493356894613 Å °0.0355098718481 Å °0.01411653126 Å °0.0182071412424 Å °0.00373249385205 Å °0.0264757992406 Å °-0.0549013552869 Å °-0.0162860175584 Å °-0.00204092013181 Å °
Refinement TLS groupSelection details: all

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more