[English] 日本語
Yorodumi- PDB-6z9d: Human Ecto-5'-nucleotidase (CD73) in complex with AOPCP derivativ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6z9d | ||||||
---|---|---|---|---|---|---|---|
Title | Human Ecto-5'-nucleotidase (CD73) in complex with AOPCP derivative AB680 (compound 55 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 / 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 / MOLECULAR REPLACEMENT / Resolution: 1.9 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 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6z9d.cif.gz | 230.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6z9d.ent.gz | 181.6 KB | Display | PDB format |
PDBx/mmJSON format | 6z9d.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z9/6z9d ftp://data.pdbj.org/pub/pdb/validation_reports/z9/6z9d | HTTPS FTP |
---|
-Related structure data
Related structure data | 6z9bC 4h2iS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-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 / Production host: Escherichia coli (E. coli) / References: UniProt: P21589, 5'-nucleotidase | ||||||||
---|---|---|---|---|---|---|---|---|---|
#2: Chemical | #3: Chemical | ChemComp-CA / | #4: Chemical | ChemComp-QDH / [[( | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.39 Å3/Da / Density % sol: 48.59 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: Crystallization buffer: 5 % PEG 6000, 0.1 M MES pH 6.0. 1 uL crystallization buffer + 1 uL of 4 mg/mL CD73 in 50 mM Tris pH 8.0, 100 mM NaCl, 10 uM ZnCl2, 1 mM AB680. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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: 1.9→78.48 Å / Num. obs: 47139 / % possible obs: 99.8 % / Redundancy: 6.2 % / Biso Wilson estimate: 35.72 Å2 / CC1/2: 0.994 / Rmerge(I) obs: 0.106 / Rpim(I) all: 0.047 / Rrim(I) all: 0.116 / Net I/σ(I): 7.4 / Num. measured all: 290273 / Scaling rejects: 159 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4H2I Resolution: 1.9→47.13 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.937 / SU R Cruickshank DPI: 0.154 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.159 / SU Rfree Blow DPI: 0.149 / SU Rfree Cruickshank DPI: 0.147
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 131.05 Å2 / Biso mean: 53.22 Å2 / Biso min: 27.06 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.32 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.9→47.13 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.9→1.91 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|