[English] 日本語
Yorodumi
- PDB-5m0e: Structure-based evolution of a hybrid steroid series of Autotaxin... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5m0e
TitleStructure-based evolution of a hybrid steroid series of Autotaxin inhibitors
ComponentsEctonucleotide pyrophosphatase/phosphodiesterase family member 2
KeywordsHYDROLASE / medicinal chemistry / structure based design / autotaxin
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 / Chem-7CR / IODIDE ION / THIOCYANATE ION / Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsKeune, W.-J. / Heidebrecht, T. / Perrakis, A.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Rational Design of Autotaxin Inhibitors by Structural Evolution of Endogenous Modulators.
Authors: Keune, W.J. / Potjewyd, F. / Heidebrecht, T. / Salgado-Polo, F. / Macdonald, S.J. / Chelvarajan, L. / Abdel Latif, A. / Soman, S. / Morris, A.J. / Watson, A.J. / Jamieson, C. / Perrakis, A.
History
DepositionOct 4, 2016Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 16, 2017Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2019Group: Data collection / Category: reflns_shell
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_struct_conn_angle / struct_asym / struct_conn / struct_conn_type / struct_site / struct_site_gen
Item: _atom_site.auth_asym_id / _atom_site.auth_seq_id ..._atom_site.auth_asym_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_entity_id / _atom_site_anisotrop.pdbx_auth_asym_id / _atom_site_anisotrop.pdbx_auth_seq_id / _atom_site_anisotrop.pdbx_label_asym_id / _chem_comp.name / _chem_comp.type / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.value / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn_type.id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Jan 17, 2024Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)99,94945
Polymers95,0381
Non-polymers4,91144
Water4,053225
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7050 Å2
ΔGint-75 kcal/mol
Surface area31490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)53.618, 61.729, 63.696
Angle α, β, γ (deg.)103.43, 98.18, 93.50
Int Tables number1
Space group name H-MP1

-
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: 95037.656 Da / Num. of mol.: 1 / Mutation: N410A, L581F, R591T, N806A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Enpp2, Atx, Npps2 / Cell line (production host): Hek293 / Organ (production host): kidney / Production host: Homo sapiens (human)
References: UniProt: Q64610, alkylglycerophosphoethanolamine phosphodiesterase
#2: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}}LINUCSPDB-CARE

-
Non-polymers , 9 types, 268 molecules

#3: Chemical ChemComp-ZN / ZINC ION


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


Mass: 126.904 Da / Num. of mol.: 14 / Source method: obtained synthetically / Formula: I
#5: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca
#6: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#7: 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
#8: Chemical ChemComp-7CR / [3,5-bis(chloranyl)phenyl]methyl 4-[(3~{R})-3-oxidanyl-3-(2-oxidanylidene-3~{H}-1,3-benzoxazol-6-yl)propyl]piperazine-1-carboxylate


Mass: 480.341 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H23Cl2N3O5
#9: Chemical
ChemComp-SCN / THIOCYANATE ION / Thiocyanate


Mass: 58.082 Da / Num. of mol.: 17 / Source method: obtained synthetically / Formula: CNS
#10: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C3H8O3
#11: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 225 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.13 Å3/Da / Density % sol: 42.13 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: PEG 3350, NaSCN and NH4I

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Jun 9, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.95→61.15 Å / Num. obs: 53155 / % possible obs: 98.8 % / Redundancy: 3.9 % / Net I/σ(I): 18.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0155refinement
XDSv1.0data reduction
Aimlessv1.0data scaling
PHASERv1.0phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2XR9

2xr9


Resolution: 1.95→61.15 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.926 / SU B: 9.288 / SU ML: 0.127 / Cross valid method: THROUGHOUT / ESU R: 0.182 / ESU R Free: 0.158 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22295 2761 4.9 %RANDOM
Rwork0.18102 ---
obs0.18309 53155 97.96 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 28.509 Å2
Baniso -1Baniso -2Baniso -3
1--0.74 Å2-0.11 Å2-0.55 Å2
2--0.62 Å20.61 Å2
3----0.01 Å2
Refinement stepCycle: 1 / Resolution: 1.95→61.15 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6238 0 200 225 6663
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0196640
X-RAY DIFFRACTIONr_bond_other_d0.0020.026033
X-RAY DIFFRACTIONr_angle_refined_deg1.6311.9738992
X-RAY DIFFRACTIONr_angle_other_deg0.98313958
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7065777
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.62123.175315
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.276151070
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.9231548
X-RAY DIFFRACTIONr_chiral_restr0.090.2949
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0217325
X-RAY DIFFRACTIONr_gen_planes_other0.0020.021563
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.0632.2113117
X-RAY DIFFRACTIONr_mcbond_other1.0462.1943098
X-RAY DIFFRACTIONr_mcangle_it1.7873.2813870
X-RAY DIFFRACTIONr_mcangle_other1.7873.2823871
X-RAY DIFFRACTIONr_scbond_it1.3072.4373523
X-RAY DIFFRACTIONr_scbond_other1.3072.4373523
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other2.1393.5645120
X-RAY DIFFRACTIONr_long_range_B_refined4.17926.0617550
X-RAY DIFFRACTIONr_long_range_B_other4.17926.0667551
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.95→2.001 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.268 207 -
Rwork0.271 3912 -
obs--96.64 %
Refinement TLS params.Method: refined / Origin x: -4.756 Å / Origin y: -45.621 Å / Origin z: 40.8326 Å
111213212223313233
T0.0033 Å2-0.0012 Å20.0021 Å2-0.0107 Å2-0.0045 Å2--0.0041 Å2
L0.4342 °20.0428 °20.2354 °2-0.4539 °20.1438 °2--0.4021 °2
S-0.0029 Å °0.0231 Å °-0.032 Å °0.0233 Å °0.0175 Å °-0.0011 Å °-0.0017 Å °-0.0181 Å °-0.0146 Å °

+
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