+Open data
-Basic information
Entry | Database: PDB / ID: 8emu | ||||||
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Title | Human Carbonic Anhydrase II Heterobifunctional Degraders | ||||||
Components | Carbonic anhydrase 2 | ||||||
Keywords | LYASE / targeted protein degrader / PROTAC / metalloenzyme | ||||||
Function / homology | Function and homology information positive regulation of cellular pH reduction / positive regulation of dipeptide transmembrane transport / regulation of monoatomic anion transport / secretion / cyanamide hydratase / cyanamide hydratase activity / arylesterase activity / regulation of chloride transport / Reversible hydration of carbon dioxide / angiotensin-activated signaling pathway ...positive regulation of cellular pH reduction / positive regulation of dipeptide transmembrane transport / regulation of monoatomic anion transport / secretion / cyanamide hydratase / cyanamide hydratase activity / arylesterase activity / regulation of chloride transport / Reversible hydration of carbon dioxide / angiotensin-activated signaling pathway / positive regulation of synaptic transmission, GABAergic / morphogenesis of an epithelium / carbonic anhydrase / regulation of intracellular pH / carbonate dehydratase activity / carbon dioxide transport / Erythrocytes take up oxygen and release carbon dioxide / Erythrocytes take up carbon dioxide and release oxygen / neuron cellular homeostasis / one-carbon metabolic process / apical part of cell / myelin sheath / zinc ion binding / extracellular exosome / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.13 Å | ||||||
Authors | Kohlbrand, A.J. / O'Herin, C.B. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Development of Human Carbonic Anhydrase II Heterobifunctional Degraders. Authors: O'Herin, C.B. / Moriuchi, Y.W. / Bemis, T.A. / Kohlbrand, A.J. / Burkart, M.D. / Cohen, S.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8emu.cif.gz | 148.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8emu.ent.gz | 94.2 KB | Display | PDB format |
PDBx/mmJSON format | 8emu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8emu_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8emu_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8emu_validation.xml.gz | 15.2 KB | Display | |
Data in CIF | 8emu_validation.cif.gz | 22 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/em/8emu ftp://data.pdbj.org/pub/pdb/validation_reports/em/8emu | HTTPS FTP |
-Related structure data
Related structure data | 8excC 8exgC 8eylC 4e49S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 29289.062 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CA2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P00918, carbonic anhydrase | ||||||
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#2: Chemical | ChemComp-ZN / | ||||||
#3: Chemical | #4: Chemical | ChemComp-MBO / | #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: 2.1 Å3/Da / Density % sol: 41.5 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop Details: 2.6-3.0 M Ammonium sulfate in 50 mM Tris-Sulfate (pH 8) |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: BRUKER AXS MICROSTAR / Wavelength: 1.54 Å |
Detector | Type: APEX II CCD / Detector: CCD / Date: Feb 11, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 1.13→40.97 Å / Num. obs: 159570 / % possible obs: 96 % / Redundancy: 5.8 % / Biso Wilson estimate: 7.84 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.091 / Net I/σ(I): 12 |
Reflection shell | Resolution: 1.13→1.17 Å / Rmerge(I) obs: 0.587 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 7193 / CC1/2: 0.752 / Rpim(I) all: 0.397 / Rrim(I) all: 0.713 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Starting model: 4.0E+49 / Resolution: 1.13→40.94 Å / SU ML: 0.1502 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 28.0355 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 13.56 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.13→40.94 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group | Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A
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