[English] 日本語
Yorodumi
- PDB-6ye2: Human Ecto-5'-nucleotidase (CD73) in complex with the AMPCP deriv... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ye2
TitleHuman Ecto-5'-nucleotidase (CD73) in complex with the AMPCP derivative A1202 (compound 4a in publication) in the closed form (crystal form IV)
Components5'-nucleotidase
KeywordsHYDROLASE / competitive nucleotide inhibitor
Function / homology
Function and homology information


thymidylate 5'-phosphatase / thymidylate 5'-phosphatase activity / ADP catabolic process / 5'-deoxynucleotidase / 5'-deoxynucleotidase activity / 7-methylguanosine nucleotidase / inhibition of non-skeletal tissue mineralization / adenosine biosynthetic process / Pyrimidine catabolism / AMP catabolic process ...thymidylate 5'-phosphatase / thymidylate 5'-phosphatase activity / ADP catabolic process / 5'-deoxynucleotidase / 5'-deoxynucleotidase activity / 7-methylguanosine nucleotidase / inhibition of non-skeletal tissue mineralization / adenosine biosynthetic process / Pyrimidine catabolism / AMP catabolic process / GMP 5'-nucleotidase activity / IMP-specific 5'-nucleotidase / IMP 5'-nucleotidase activity / Nicotinate metabolism / Purine catabolism / XMP 5'-nucleosidase activity / 5'-nucleotidase / 5'-nucleotidase activity / DNA metabolic process / leukocyte cell-cell adhesion / response to ATP / response to inorganic substance / calcium ion homeostasis / Purinergic signaling in leishmaniasis infection / ATP metabolic process / negative regulation of inflammatory response / external side of plasma membrane / nucleotide binding / cell surface / extracellular exosome / zinc ion binding / nucleoplasm / membrane / identical protein binding / plasma membrane / cytosol
Similarity search - Function
5'-nucleotidase signature 1. / 5'-Nucleotidase, conserved site / 5'-nucleotidase signature 2. / 5'-Nucleotidase, C-terminal / 5'-nucleotidase, C-terminal domain / 5'-Nucleotidase/apyrase / 5'-Nucleotidase, C-terminal domain superfamily / Calcineurin-like phosphoesterase domain, ApaH type / Calcineurin-like phosphoesterase / Metallo-dependent phosphatase-like
Similarity search - Domain/homology
Chem-OO5 / 5'-nucleotidase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.44 Å
Model detailsThe compound is a competitive non-nucleotide inhibitor binding to the active site
AuthorsScaletti, E. / Strater, N.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Discovery of Potent and Selective Methylenephosphonic Acid CD73 Inhibitors.
Authors: Sharif, E.U. / Kalisiak, J. / Lawson, K.V. / Miles, D.H. / Newcomb, E. / Lindsey, E.A. / Rosen, B.R. / Debien, L.P.P. / Chen, A. / Zhao, X. / Young, S.W. / Walker, N.P. / Strater, N. / ...Authors: Sharif, E.U. / Kalisiak, J. / Lawson, K.V. / Miles, D.H. / Newcomb, E. / Lindsey, E.A. / Rosen, B.R. / Debien, L.P.P. / Chen, A. / Zhao, X. / Young, S.W. / Walker, N.P. / Strater, N. / Scaletti, E.R. / Jin, L. / Xu, G. / Leleti, M.R. / Powers, J.P.
History
DepositionMar 23, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 20, 2021Provider: repository / Type: Initial release
Revision 1.1Jan 27, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 5'-nucleotidase
B: 5'-nucleotidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,79010
Polymers118,5212
Non-polymers1,2698
Water10,449580
1
A: 5'-nucleotidase
hetero molecules

B: 5'-nucleotidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,79010
Polymers118,5212
Non-polymers1,2698
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_456x-1/2,-y+1/2,-z+11
Buried area2960 Å2
ΔGint-126 kcal/mol
Surface area39630 Å2
MethodPISA
Unit cell
Length a, b, c (Å)93.360, 230.940, 53.970
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212

-
Components

#1: Protein 5'-nucleotidase / / 5'-NT / Ecto-5'-nucleotidase


Mass: 59260.406 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NT5E, NT5, NTE / Production host: Escherichia coli (E. coli) / References: UniProt: P21589, 5'-nucleotidase
#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-OO5 / [(2~{R},3~{S},4~{R},5~{R})-5-[6-chloranyl-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxymethylphosphonic acid


Mass: 463.810 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H23ClN5O7P / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-CA / CALCIUM ION


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


Mass: 18.015 Da / Num. of mol.: 580 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.45 Å3/Da / Density % sol: 49.89 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 1 mM ZnCl2, 11-14% PEG6000, 15 % Glycerol, 100 mM sodium citrate pH 5.4-5.6
PH range: 5.4-5.6

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.2 / Wavelength: 0.91826 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Oct 5, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91826 Å / Relative weight: 1
ReflectionResolution: 2.44→46.73 Å / Num. obs: 44292 / % possible obs: 99.4 % / Redundancy: 4.419 % / Biso Wilson estimate: 48.59 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.114 / Rrim(I) all: 0.13 / Χ2: 0.949 / Net I/σ(I): 11.24 / Num. measured all: 195708
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.44-2.594.4260.8221.9531091710470240.8280.93698.9
2.59-2.764.2940.5272.9928280663565860.9240.60299.3
2.76-2.984.5920.3654.4928542623962160.9550.41399.6
2.98-3.274.6240.2256.9626380572357050.9830.25499.7
3.27-3.654.4410.1211.6823089521151990.9930.13799.8
3.65-4.214.1630.06618.0419300466146360.9970.07699.5
4.21-5.154.5920.04526.8618143396739510.9990.05199.6
5.15-7.244.2070.04824.3513155314331270.9980.05599.5
7.24-46.734.1820.02638.087728189018480.9990.0397.8

-
Processing

Software
NameVersionClassification
XDSdata scaling
BUSTER2.10.3refinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
BUSTER2.10.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6YE1

6ye1


Resolution: 2.44→46.73 Å / Cor.coef. Fo:Fc: 0.937 / Cor.coef. Fo:Fc free: 0.905 / SU R Cruickshank DPI: 0.411 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.495 / SU Rfree Blow DPI: 0.254 / SU Rfree Cruickshank DPI: 0.249
RfactorNum. reflection% reflectionSelection details
Rfree0.23 2100 4.74 %RANDOM
Rwork0.175 ---
obs0.178 44291 99.4 %-
Displacement parametersBiso max: 164.9 Å2 / Biso mean: 56.66 Å2 / Biso min: 21.59 Å2
Baniso -1Baniso -2Baniso -3
1--18.811 Å20 Å20 Å2
2--14.7083 Å20 Å2
3---4.1027 Å2
Refine analyzeLuzzati coordinate error obs: 0.3 Å
Refinement stepCycle: final / Resolution: 2.44→46.73 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8069 0 66 580 8715
Biso mean--57.17 51.93 -
Num. residues----1036
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d2918SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1435HARMONIC5
X-RAY DIFFRACTIONt_it8322HARMONIC20
X-RAY DIFFRACTIONt_nbd3SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1066SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact9973SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d8322HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg11282HARMONIC21.18
X-RAY DIFFRACTIONt_omega_torsion3.47
X-RAY DIFFRACTIONt_other_torsion19.6
LS refinement shellResolution: 2.44→2.46 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.3492 42 4.74 %
Rwork0.2462 844 -
all0.2511 886 -
obs--95.49 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
12.68130.9250.48513.05860.20841.40410.07360.4406-0.07270.26160.0343-0.2187-0.01850.0927-0.10790.0650.0613-0.0357-0.1230.0103-0.249123.102511.23058.3884
20.5148-0.88090.33645.7969-0.0622.30340.20850.11650.1918-0.5442-0.2092-0.54420.06620.03860.00070.17920.01960.1035-0.27520.1247-0.227522.404842.27654.848
31.5804-0.09880.12337.63381.16083.4390.05280.24060.014-0.1134-0.1565-0.0634-0.0532-0.11180.1037-0.15280.07450.0262-0.24610.0459-0.30468.368920.920635.209
40.1286-1.08710.04637.9506-0.54562.33470.13630.07950.0818-0.5442-0.1359-0.5442-0.115-0.009-0.00040.19480.05930.067-0.3040.1027-0.227868.569551.679431.7741
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{A|1 - A|333}A1 - 333
2X-RAY DIFFRACTION2{A|334 - A|1000 }A334 - 1000
3X-RAY DIFFRACTION3{B|1 - B|333}B1 - 333
4X-RAY DIFFRACTION4{B|334 - B|1000 }B334 - 1000

+
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