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Yorodumi- PDB-6z9b: Human Ecto-5'-nucleotidase (CD73) in complex with AOPCP derivativ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6z9b | ||||||
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Title | Human Ecto-5'-nucleotidase (CD73) in complex with AOPCP derivative A830 (compound 16 in publication) in the closed form (crystal form III) | ||||||
Components | 5'-nucleotidase | ||||||
Keywords | HYDROLASE / zinc enzyme / nucleotide analog / inhibitor / Arcus Biosciences | ||||||
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 / : / Purinergic signaling in leishmaniasis infection / calcium ion homeostasis / ATP metabolic process / negative regulation of inflammatory response / external side of plasma membrane / nucleotide binding / cell surface / zinc ion binding / extracellular exosome / nucleoplasm / identical protein binding / membrane / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.17 Å | ||||||
Model details | The compound is a competitive non-nucleotide inhibitor binding to the active site | ||||||
Authors | Strater, N. / Scaletti, E. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Discovery of AB680: A Potent and Selective Inhibitor of CD73. Authors: Lawson, K.V. / Kalisiak, J. / Lindsey, E.A. / Newcomb, E.T. / Leleti, M.R. / Debien, L. / Rosen, B.R. / Miles, D.H. / Sharif, E.U. / Jeffrey, J.L. / Tan, J.B.L. / Chen, A. / Zhao, S. / Xu, G. ...Authors: Lawson, K.V. / Kalisiak, J. / Lindsey, E.A. / Newcomb, E.T. / Leleti, M.R. / Debien, L. / Rosen, B.R. / Miles, D.H. / Sharif, E.U. / Jeffrey, J.L. / Tan, J.B.L. / Chen, A. / Zhao, S. / Xu, G. / Fu, L. / Jin, L. / Park, T.W. / Berry, W. / Moschutz, S. / Scaletti, E. / Strater, N. / Walker, N.P. / Young, S.W. / Walters, M.J. / Schindler, U. / Powers, J.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6z9b.cif.gz | 230 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6z9b.ent.gz | 180.4 KB | Display | PDB format |
PDBx/mmJSON format | 6z9b.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6z9b_validation.pdf.gz | 801.8 KB | Display | wwPDB validaton report |
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Full document | 6z9b_full_validation.pdf.gz | 804.2 KB | Display | |
Data in XML | 6z9b_validation.xml.gz | 22.7 KB | Display | |
Data in CIF | 6z9b_validation.cif.gz | 33.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z9/6z9b ftp://data.pdbj.org/pub/pdb/validation_reports/z9/6z9b | HTTPS FTP |
-Related structure data
Related structure data | 6z9dC 4h2iS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 59260.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: CD73 Construct 4.0 for E. coli expression and refolding Source: (gene. exp.) Homo sapiens (human) / Gene: NT5E, NT5, NTE / Production host: Escherichia coli (E. coli) / References: UniProt: P21589, 5'-nucleotidase | ||||||||
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#2: Chemical | #3: Chemical | ChemComp-CA / | #4: Chemical | ChemComp-QCQ / [[( | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.55 Å3/Da / Density % sol: 51.71 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 5.5 Details: CD73 at 7 mg/mL was incubated on ice for one hour with 1mM of the inhibitor and 0.1 mM ZnCl2. 1 uL of protein was mixed with 1 uL of 11-14% PEG6000 and 100 mM sodium citrate pH 5.4-5.6. For ...Details: CD73 at 7 mg/mL was incubated on ice for one hour with 1mM of the inhibitor and 0.1 mM ZnCl2. 1 uL of protein was mixed with 1 uL of 11-14% PEG6000 and 100 mM sodium citrate pH 5.4-5.6. For cryoprotection glycerol was added to a final concentration of 15 % to the reservoir buffer. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.9184 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 24, 2016 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9184 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.17→48.23 Å / Num. obs: 32496 / % possible obs: 99.2 % / Redundancy: 6.425 % / Biso Wilson estimate: 32.78 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.223 / Rrim(I) all: 0.243 / Χ2: 0.803 / Net I/σ(I): 8.61 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: pdbid 4H2I Resolution: 2.17→48.23 Å / Cor.coef. Fo:Fc: 0.921 / Cor.coef. Fo:Fc free: 0.881 / SU R Cruickshank DPI: 0.245 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.26 / SU Rfree Blow DPI: 0.213 / SU Rfree Cruickshank DPI: 0.21
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Displacement parameters | Biso max: 131.03 Å2 / Biso mean: 42.75 Å2 / Biso min: 18.89 Å2
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Refine analyze | Luzzati coordinate error obs: 0.33 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.17→48.23 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.17→2.18 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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