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Yorodumi- PDB-6xuq: Human Ecto-5'-nucleotidase (CD73) in complex with A1618 (compound... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6xuq | ||||||
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Title | Human Ecto-5'-nucleotidase (CD73) in complex with A1618 (compound 1b in publication) in the closed state in crystal form III | ||||||
Components | 5'-nucleotidase | ||||||
Keywords | HYDROLASE / non-nucleotide 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 / 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.97 Å | ||||||
Model details | The compound is a competitive non-nucleotide inhibitor binding to the active site | ||||||
Authors | Strater, N. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Discovery of Potent and Selective Non-Nucleotide Small Molecule Inhibitors of CD73. Authors: Beatty, J.W. / Lindsey, E.A. / Thomas-Tran, R. / Debien, L. / Mandal, D. / Jeffrey, J.L. / Tran, A.T. / Fournier, J. / Jacob, S.D. / Yan, X. / Drew, S.L. / Ginn, E. / Chen, A. / Pham, A.T. / ...Authors: Beatty, J.W. / Lindsey, E.A. / Thomas-Tran, R. / Debien, L. / Mandal, D. / Jeffrey, J.L. / Tran, A.T. / Fournier, J. / Jacob, S.D. / Yan, X. / Drew, S.L. / Ginn, E. / Chen, A. / Pham, A.T. / Zhao, S. / Jin, L. / Young, S.W. / Walker, N.P. / Leleti, M.R. / Moschutz, S. / Strater, N. / Powers, J.P. / Lawson, K.V. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6xuq.cif.gz | 227.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6xuq.ent.gz | 179.5 KB | Display | PDB format |
PDBx/mmJSON format | 6xuq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xu/6xuq ftp://data.pdbj.org/pub/pdb/validation_reports/xu/6xuq | HTTPS FTP |
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-Related structure data
Related structure data | 6xueC 6xugC 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: 61701.074 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: CD73 construct 8.0 / Source: (gene. exp.) Homo sapiens (human) / Gene: NT5E, NT5, NTE / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P21589, 5'-nucleotidase | ||||||||
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#2: Chemical | #3: Chemical | ChemComp-CA / | #4: Chemical | ChemComp-O1T / [[( | #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: 2.38 Å3/Da / Density % sol: 48.29 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 8 Details: Reservoir: 7.5 % PEG 6.000, 0.1 M MES pH 6.2. Drop: 1 micro-L crystallization buffer + 1 micro-L of 3 mg/mL CD73 in 10 mM Tris pH 8.0, 10 micro-M ZnCl2 and 1 mM of compound. Cryo: 20% PEG200 ...Details: Reservoir: 7.5 % PEG 6.000, 0.1 M MES pH 6.2. Drop: 1 micro-L crystallization buffer + 1 micro-L of 3 mg/mL CD73 in 10 mM Tris pH 8.0, 10 micro-M ZnCl2 and 1 mM of compound. Cryo: 20% PEG200 in crystallization drop |
-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: 0.91841 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 2, 2018 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.91841 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.97→47.13 Å / Num. obs: 80202 / % possible obs: 99.6 % / Redundancy: 3.482 % / Biso Wilson estimate: 53.22 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.12 / Rrim(I) all: 0.142 / Χ2: 1.163 / Net I/σ(I): 6.81 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 4h2i Resolution: 1.97→46.21 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.938 / SU R Cruickshank DPI: 0.172 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.175 / SU Rfree Blow DPI: 0.15 / SU Rfree Cruickshank DPI: 0.149
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Displacement parameters | Biso max: 148.14 Å2 / Biso mean: 67.82 Å2 / Biso min: 13.57 Å2
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Refine analyze | Luzzati coordinate error obs: 0.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.97→46.21 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.97→1.98 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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Refinement TLS params. | Method: refined / Origin x: -20.199 Å / Origin y: 20.1271 Å / Origin z: -29.1902 Å
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Refinement TLS group | Selection details: { A|* } |