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Yorodumi- PDB-4qag: Structure of a dihydroxycoumarin active-site inhibitor in complex... -
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-Basic information
Entry | Database: PDB / ID: 4qag | |||||||||
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Title | Structure of a dihydroxycoumarin active-site inhibitor in complex with the RNASE H domain of HIV-1 reverse transcriptase | |||||||||
Components | Reverse transcriptase/ribonuclease H | |||||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / RNASE H INHIBITOR / STRUCTURE-BASED DRUG DESIGN / ACTIVE SITE / TRANSFERASE / DIHYDROXYCOUMARIN ANALOGS / DIHYDROXY-BENZOPYRONE DERIVATIVES / DIVALENT CATION CHELATOR / AIDS / REVERSE TRANSCRIPTASE / PROTEIN-INHIBITOR COMPLEX / HYDROLASE-HYDROLASE INHIBITOR complex | |||||||||
Function / homology | Function and homology information HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency ...HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency / viral penetration into host nucleus / RNA stem-loop binding / symbiont-mediated suppression of host gene expression / RNA-directed DNA polymerase activity / host cell / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / viral nucleocapsid / aspartic-type endopeptidase activity / DNA recombination / DNA-directed DNA polymerase / Hydrolases; Acting on ester bonds / DNA-directed DNA polymerase activity / symbiont entry into host cell / lipid binding / host cell nucleus / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis / DNA binding / zinc ion binding / membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus type 1 | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.712 Å | |||||||||
Authors | Himmel, D.M. / Ho, W.C. / Arnold, E. | |||||||||
Citation | Journal: J.Mol.Biol. / Year: 2014 Title: Structure of a Dihydroxycoumarin Active-Site Inhibitor in Complex with the RNase H Domain of HIV-1 Reverse Transcriptase and Structure-Activity Analysis of Inhibitor Analogs. Authors: Himmel, D.M. / Myshakina, N.S. / Ilina, T. / Van Ry, A. / Ho, W.C. / Parniak, M.A. / Arnold, E. #1: Journal: Structure / Year: 2009 Title: Structure of HIV-1 Reverse Transcriptase with the Inhibitor beta-Thujaplicinol Bound at the RNase H Active Site Authors: Himmel, D.M. / Maegley, K.A. / Pauly, T.A. / Bauman, J.D. / Das, K. / Dharia, C. / Clark Jr., A.D. / Ryan, K. / Hickey, M.J. / Love, R.A. / Hughes, S.H. / Bergqvist, S. / Arnold, E. #2: Journal: J.Med.Chem. / Year: 2011 Title: Synthesis, Activity, and Structural Analysis of Novel ALPHA-HYDROXYTROPOLONE INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REVERSE TRANSCRIPTASE-ASSOCIATED RIBONUCLEASE H Authors: Chung, S. / Himmel, D.M. / Jiang, J. / Wojtak, K. / Bauman, J.D. / Rausch, J.W. / Wilson, J.A. / Beutler, J.A. / Thomas, C.J. / Arnold, E. / Le Grice, S.F.J. #3: Journal: Proc.Natl.Acad.Sci.USA / Year: 2008 Title: HIGH-RESOLUTION STRUCTURES OF HIV-1 REVERSE TRANSCRIPTASE/TMC278 COMPLEXES: STRATEGIC FLEXIBILITY EXPLAINS POTENCY AGAINST RESISTANCE MUTATIONS Authors: Das, K. / Bauman, J.D. / Clark Jr., A.D. / Frenkel, Y.V. / Lewi, P.J. / Shatkin, A.J. / Hughes, S.H. / Arnold, E. #4: Journal: ACS CHEM.BIOL. / Year: 2006 Title: HIV-1 REVERSE TRANSCRIPTASE STRUCTURE WITH RNASE H INHIBITOR DIHYDROXY BENZOYL NAPHTHYL HYDRAZONE BOUND AT A NOVEL SITE Authors: Himmel, D.M. / Sarafianos, S.G. / Dharmasena, S. / Hossain, M.M. / McCoy-Simandle, K. / Ilina, T. / Clark Jr., A.D. / Knight, J.L. / Julias, J.G. / Clark, P.K. / Krogh-Jespersen, K. / Levy, ...Authors: Himmel, D.M. / Sarafianos, S.G. / Dharmasena, S. / Hossain, M.M. / McCoy-Simandle, K. / Ilina, T. / Clark Jr., A.D. / Knight, J.L. / Julias, J.G. / Clark, P.K. / Krogh-Jespersen, K. / Levy, R.M. / Hughes, S.H. / Parniak, M.A. / Arnold, E. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4qag.cif.gz | 131.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4qag.ent.gz | 100.6 KB | Display | PDB format |
PDBx/mmJSON format | 4qag.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4qag_validation.pdf.gz | 453 KB | Display | wwPDB validaton report |
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Full document | 4qag_full_validation.pdf.gz | 456.4 KB | Display | |
Data in XML | 4qag_validation.xml.gz | 14.7 KB | Display | |
Data in CIF | 4qag_validation.cif.gz | 20.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qa/4qag ftp://data.pdbj.org/pub/pdb/validation_reports/qa/4qag | HTTPS FTP |
-Related structure data
Related structure data | 3ig1S S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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3 |
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Unit cell |
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-Components
#1: Protein | Mass: 14714.667 Da / Num. of mol.: 2 / Fragment: UNP residues 1024-1156 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 / Gene: gag-pol / Plasmid: pLysS / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) References: UniProt: P03366, RNA-directed DNA polymerase, DNA-directed DNA polymerase, retroviral ribonuclease H, exoribonuclease H #2: Chemical | ChemComp-MN / #3: Chemical | #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.88 Å3/Da / Density % sol: 57.27 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.2 Details: 100 mM Bicine pH 8.2, 10 mM Manganese Sulfate, 1 mM Sodium Azide, 9% PEG 3350, combined with equal volume of 10 mM Tris pH 8.0, 75 mM NaCl, 20 mg/mL (1.34 mM) RNase H, VAPOR DIFFUSION, ...Details: 100 mM Bicine pH 8.2, 10 mM Manganese Sulfate, 1 mM Sodium Azide, 9% PEG 3350, combined with equal volume of 10 mM Tris pH 8.0, 75 mM NaCl, 20 mg/mL (1.34 mM) RNase H, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: NSLS / Beamline: X25 / Wavelength: 1.1 / Wavelength: 1.1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jun 3, 2010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Redundancy: 7.8 % / Number: 272419 / Rmerge(I) obs: 0.088 / Χ2: 1 / D res high: 1.71 Å / D res low: 40 Å / Num. obs: 34856 / % possible obs: 98.5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diffraction reflection shell |
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Reflection | Resolution: 1.71→40 Å / Num. all: 35387 / Num. obs: 34856 / % possible obs: 98.5 % / Observed criterion σ(I): -0.4 / Redundancy: 7.8 % / Biso Wilson estimate: 34.341 Å2 / Rmerge(I) obs: 0.088 / Rsym value: 0.088 / Χ2: 1.003 / Net I/σ(I): 27.1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Rfactor: 38.45 / Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3IG1 Resolution: 1.712→28.565 Å / SU ML: 0.23 / Isotropic thermal model: ANISOTROPIC / Cross valid method: THROUGHOUT / σ(F): 0 / Phase error: 26.88 / Stereochemistry target values: Engh & Huber
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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 max: 159.53 Å2 / Biso mean: 56.6933 Å2 / Biso min: 30.35 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error free: 0.23 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.712→28.565 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 7
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