+Open data
-Basic information
Entry | Database: PDB / ID: 6uni | ||||||
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Title | Human CYP3A4 bound to an inhibitor | ||||||
Components | Cytochrome P450 3A4 | ||||||
Keywords | OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / CYP3A4 / inhibitor / complex / OXIDOREDUCTASE / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex | ||||||
Function / homology | Function and homology information quinine 3-monooxygenase / 1,8-cineole 2-exo-monooxygenase / albendazole monooxygenase (sulfoxide-forming) / quinine 3-monooxygenase activity / 1,8-cineole 2-exo-monooxygenase activity / 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity / vitamin D3 25-hydroxylase activity / testosterone 6-beta-hydroxylase activity / vitamin D 24-hydroxylase activity / vitamin D catabolic process ...quinine 3-monooxygenase / 1,8-cineole 2-exo-monooxygenase / albendazole monooxygenase (sulfoxide-forming) / quinine 3-monooxygenase activity / 1,8-cineole 2-exo-monooxygenase activity / 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity / vitamin D3 25-hydroxylase activity / testosterone 6-beta-hydroxylase activity / vitamin D 24-hydroxylase activity / vitamin D catabolic process / retinoic acid 4-hydroxylase activity / aflatoxin metabolic process / caffeine oxidase activity / estrogen 16-alpha-hydroxylase activity / estrogen 2-hydroxylase activity / lipid hydroxylation / anandamide 8,9 epoxidase activity / anandamide 11,12 epoxidase activity / anandamide 14,15 epoxidase activity / alkaloid catabolic process / Aflatoxin activation and detoxification / Biosynthesis of maresin-like SPMs / monoterpenoid metabolic process / vitamin D metabolic process / Atorvastatin ADME / oxidative demethylation / : / steroid catabolic process / Xenobiotics / Phase I - Functionalization of compounds / long-chain fatty acid biosynthetic process / estrogen metabolic process / retinol metabolic process / retinoic acid metabolic process / Prednisone ADME / unspecific monooxygenase / aromatase activity / Aspirin ADME / steroid metabolic process / androgen metabolic process / steroid hydroxylase activity / xenobiotic catabolic process / monooxygenase activity / steroid binding / cholesterol metabolic process / xenobiotic metabolic process / lipid metabolic process / oxygen binding / oxidoreductase activity / iron ion binding / intracellular membrane-bounded organelle / heme binding / endoplasmic reticulum membrane / enzyme binding / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.602 Å | ||||||
Authors | Sevrioukova, I.F. | ||||||
Funding support | United States, 1items
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Citation | Journal: Bioorg.Med.Chem. / Year: 2020 Title: An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4. Authors: Samuels, E.R. / Sevrioukova, I.F. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6uni.cif.gz | 202.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6uni.ent.gz | 159.9 KB | Display | PDB format |
PDBx/mmJSON format | 6uni.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6uni_validation.pdf.gz | 433.9 KB | Display | wwPDB validaton report |
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Full document | 6uni_full_validation.pdf.gz | 437.1 KB | Display | |
Data in XML | 6uni_validation.xml.gz | 2.3 KB | Display | |
Data in CIF | 6uni_validation.cif.gz | 6.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/un/6uni ftp://data.pdbj.org/pub/pdb/validation_reports/un/6uni | HTTPS FTP |
-Related structure data
Related structure data | 6uneC 6ungC 6unhC 6unjC 6unkC 6unlC 6unmC 5vccS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 55757.812 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CYP3A4, CYP3A3 / Plasmid: pcWori / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / Variant (production host): C41 References: UniProt: P08684, unspecific monooxygenase, 1,8-cineole 2-exo-monooxygenase, albendazole monooxygenase (sulfoxide-forming), quinine 3-monooxygenase |
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#2: Chemical | ChemComp-HEM / |
#3: Chemical | ChemComp-QDV / |
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: 2.09 Å3/Da / Density % sol: 41.11 % |
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Crystal grow | Temperature: 298 K / Method: microbatch / Details: PEG 3350, sodium malonate / PH range: 6.0-7.0 |
-Data collection
Diffraction | Mean temperature: 77 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL14-1 / Wavelength: 1.195 Å | ||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Jul 18, 2018 / Details: mirrors | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.195 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.6→39.25 Å / Num. obs: 15084 / % possible obs: 99.6 % / Redundancy: 5.6 % / Biso Wilson estimate: 102.95 Å2 / CC1/2: 0.613 / Rmerge(I) obs: 0.043 / Rpim(I) all: 0.025 / Rrim(I) all: 0.05 / Net I/σ(I): 14.6 / Num. measured all: 84808 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5VCC Resolution: 2.602→39.249 Å / SU ML: 0.43 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 31.52
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 272.79 Å2 / Biso mean: 134.6637 Å2 / Biso min: 64.33 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.602→39.249 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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Refinement TLS params. | Method: refined / Origin x: -19.3769 Å / Origin y: -27.0015 Å / Origin z: -12.9278 Å
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Refinement TLS group |
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