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Yorodumi- PDB-3hnc: Crystal structure of human ribonucleotide reductase 1 bound to th... -
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-Basic information
Entry | Database: PDB / ID: 3hnc | ||||||
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Title | Crystal structure of human ribonucleotide reductase 1 bound to the effector TTP | ||||||
Components | Ribonucleoside-diphosphate reductase large subunit | ||||||
Keywords | OXIDOREDUCTASE / ribonucleotide reductase / Allosteric enzyme / ATP-binding / DNA replication / Nucleotide-binding | ||||||
Function / homology | Function and homology information ribonucleoside-diphosphate reductase activity / pyrimidine nucleobase metabolic process / cell proliferation in forebrain / ribonucleoside diphosphate metabolic process / positive regulation of G0 to G1 transition / mitochondrial DNA replication / 2'-deoxyribonucleotide biosynthetic process / ribonucleoside-diphosphate reductase complex / ribonucleoside-diphosphate reductase / ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor ...ribonucleoside-diphosphate reductase activity / pyrimidine nucleobase metabolic process / cell proliferation in forebrain / ribonucleoside diphosphate metabolic process / positive regulation of G0 to G1 transition / mitochondrial DNA replication / 2'-deoxyribonucleotide biosynthetic process / ribonucleoside-diphosphate reductase complex / ribonucleoside-diphosphate reductase / ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor / Interconversion of nucleotide di- and triphosphates / deoxyribonucleotide biosynthetic process / protein heterotetramerization / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of G2/M transition of mitotic cell cycle / response to ionizing radiation / DNA synthesis involved in DNA repair / cell projection / nuclear envelope / male gonad development / disordered domain specific binding / retina development in camera-type eye / DNA repair / neuronal cell body / mitochondrion / ATP binding / identical protein binding / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.41 Å | ||||||
Authors | Fairman, J.W. / Wijerathna, S.R. / Xu, H. / Dealwis, C.G. | ||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2011 Title: Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization. Authors: James Wesley Fairman / Sanath Ranjan Wijerathna / Md Faiz Ahmad / Hai Xu / Ryo Nakano / Shalini Jha / Jay Prendergast / R Martin Welin / Susanne Flodin / Annette Roos / Pär Nordlund / ...Authors: James Wesley Fairman / Sanath Ranjan Wijerathna / Md Faiz Ahmad / Hai Xu / Ryo Nakano / Shalini Jha / Jay Prendergast / R Martin Welin / Susanne Flodin / Annette Roos / Pär Nordlund / Zongli Li / Thomas Walz / Chris Godfrey Dealwis / Abstract: Ribonucleotide reductase (RR) is an α(n)β(n) (RR1-RR2) complex that maintains balanced dNTP pools by reducing NDPs to dNDPs. RR1 is the catalytic subunit, and RR2 houses the free radical required ...Ribonucleotide reductase (RR) is an α(n)β(n) (RR1-RR2) complex that maintains balanced dNTP pools by reducing NDPs to dNDPs. RR1 is the catalytic subunit, and RR2 houses the free radical required for catalysis. RR is allosterically regulated by its activator ATP and its inhibitor dATP, which regulate RR activity by inducing oligomerization of RR1. Here, we report the first X-ray structures of human RR1 bound to TTP alone, dATP alone, TTP-GDP, TTP-ATP, and TTP-dATP. These structures provide insights into regulation of RR by ATP or dATP. At physiological dATP concentrations, RR1 forms inactive hexamers. We determined the first X-ray structure of the RR1-dATP hexamer and used single-particle electron microscopy to visualize the α(6)-ββ'-dATP holocomplex. Site-directed mutagenesis and functional assays confirm that hexamerization is a prerequisite for inhibition by dATP. Our data indicate a mechanism for regulating RR activity by dATP-induced oligomerization. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3hnc.cif.gz | 573.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3hnc.ent.gz | 471.7 KB | Display | PDB format |
PDBx/mmJSON format | 3hnc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3hnc_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 3hnc_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 3hnc_validation.xml.gz | 54.5 KB | Display | |
Data in CIF | 3hnc_validation.cif.gz | 76 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hn/3hnc ftp://data.pdbj.org/pub/pdb/validation_reports/hn/3hnc | HTTPS FTP |
-Related structure data
Related structure data | 1807C 2wghC 3hndC 3hneC 3hnfC 3pawC 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: 90179.023 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RR1, RRM1 / Plasmid: pET21 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)RIL References: UniProt: P23921, ribonucleoside-diphosphate reductase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-SO4 / #5: 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: 2.39 Å3/Da / Density % sol: 48.59 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.9 Details: 0.1 M Tris-HCl pH 7.9, 0.2 M LiSO4, 19% PEG 3350, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 0.9 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Apr 15, 2008 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.3→40 Å / Num. obs: 75994 / % possible obs: 97.8 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.091 / Χ2: 1.221 / Net I/σ(I): 13.144 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.41→39.53 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.926 / Occupancy max: 1 / Occupancy min: 0 / SU B: 16.325 / SU ML: 0.19 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.408 / ESU R Free: 0.256 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 85.11 Å2 / Biso mean: 46.798 Å2 / Biso min: 20 Å2
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Refinement step | Cycle: LAST / Resolution: 2.41→39.53 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.41→2.48 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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