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Yorodumi- PDB-3cd7: Thermodynamic and structure guided design of statin hmg-coa reduc... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3cd7 | ||||||
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Title | Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors | ||||||
Components | 3-hydroxy-3-methylglutaryl-coenzyme A reductase | ||||||
Keywords | OXIDOREDUCTASE / CHOLESTEROL BIOSYNTHESIS / HMG-COA / NADPH / STATIN / Alternative splicing / Endoplasmic reticulum / Glycoprotein / Lipid synthesis / Membrane / Peroxisome / Polymorphism / Steroid biosynthesis / Transmembrane | ||||||
Function / homology | Function and homology information hydroxymethylglutaryl-CoA reductase (NADPH) / hydroxymethylglutaryl-CoA reductase (NADPH) activity / sterol biosynthetic process / GTPase regulator activity / coenzyme A binding / negative regulation of amyloid-beta clearance / Cholesterol biosynthesis / EGR2 and SOX10-mediated initiation of Schwann cell myelination / coenzyme A metabolic process / isoprenoid biosynthetic process ...hydroxymethylglutaryl-CoA reductase (NADPH) / hydroxymethylglutaryl-CoA reductase (NADPH) activity / sterol biosynthetic process / GTPase regulator activity / coenzyme A binding / negative regulation of amyloid-beta clearance / Cholesterol biosynthesis / EGR2 and SOX10-mediated initiation of Schwann cell myelination / coenzyme A metabolic process / isoprenoid biosynthetic process / peroxisomal membrane / cholesterol biosynthetic process / negative regulation of protein secretion / regulation of ERK1 and ERK2 cascade / NADPH binding / Activation of gene expression by SREBF (SREBP) / negative regulation of protein catabolic process / long-term synaptic potentiation / PPARA activates gene expression / visual learning / endoplasmic reticulum membrane / endoplasmic reticulum Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.05 Å | ||||||
Authors | Pavlovsky, A. / Sarver, R.W. / Harris, M.S. / Finzel, B.C. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2008 Title: Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme a reductase. Authors: Sarver, R.W. / Bills, E. / Bolton, G. / Bratton, L.D. / Caspers, N.L. / Dunbar, J.B. / Harris, M.S. / Hutchings, R.H. / Kennedy, R.M. / Larsen, S.D. / Pavlovsky, A. / Pfefferkorn, J.A. / Bainbridge, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3cd7.cif.gz | 312.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3cd7.ent.gz | 251.7 KB | Display | PDB format |
PDBx/mmJSON format | 3cd7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3cd7_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 3cd7_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 3cd7_validation.xml.gz | 59.8 KB | Display | |
Data in CIF | 3cd7_validation.cif.gz | 83.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cd/3cd7 ftp://data.pdbj.org/pub/pdb/validation_reports/cd/3cd7 | HTTPS FTP |
-Related structure data
Related structure data | 3cctC 3ccwC 3cczC 3cd0C 3cd5C 3cdaC 3cdbC 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: 47479.551 Da / Num. of mol.: 4 / Fragment: CATALYTIC DOMAIN (RESIDUES 441-875) / Mutation: M485I Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HMGCR / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 STAR References: UniProt: P04035, hydroxymethylglutaryl-CoA reductase (NADPH) #2: Chemical | ChemComp-882 / ( #3: 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: 2.34 Å3/Da / Density % sol: 47.45 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8 Details: protein 15-20 mg/ml, Ligand (saturated),PEG 4000, MgCl2 0.2M, Tris-HCL pH8 0.1M, 7-10 days, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Apr 19, 2003 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Av σ(I) over netI: 9.5 / Number: 223133 / Rmerge(I) obs: 0.081 / Χ2: 0.88 / D res high: 2.06 Å / D res low: 30 Å / Num. obs: 79035 / % possible obs: 73.6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diffraction reflection shell |
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Reflection | Resolution: 2.05→30 Å / Num. obs: 79035 / % possible obs: 73.6 % / Rmerge(I) obs: 0.081 / Χ2: 0.884 / Net I/σ(I): 9.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 2.05→30 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.912 / SU B: 6.25 / SU ML: 0.162 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.313 / ESU R Free: 0.231 / 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: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 33.134 Å2
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Refinement step | Cycle: LAST / Resolution: 2.05→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.051→2.105 Å / Total num. of bins used: 20
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