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Yorodumi- PDB-5t9u: Discovery of a Potent Cyclophilin Inhibitor (Compound 3) based on... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5t9u | ||||||
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Title | Discovery of a Potent Cyclophilin Inhibitor (Compound 3) based on Structural Simplification of Sanglifehrin A | ||||||
Components | Peptidyl-prolyl cis-trans isomerase A | ||||||
Keywords | isomerase/isomerase inhibitor / cyclophilin inhibitor antiviral HCV / isomerase-isomerase inhibitor complex | ||||||
Function / homology | Function and homology information negative regulation of protein K48-linked ubiquitination / negative regulation of viral life cycle / regulation of apoptotic signaling pathway / cell adhesion molecule production / lipid droplet organization / heparan sulfate binding / regulation of viral genome replication / virion binding / leukocyte chemotaxis / endothelial cell activation ...negative regulation of protein K48-linked ubiquitination / negative regulation of viral life cycle / regulation of apoptotic signaling pathway / cell adhesion molecule production / lipid droplet organization / heparan sulfate binding / regulation of viral genome replication / virion binding / leukocyte chemotaxis / endothelial cell activation / negative regulation of stress-activated MAPK cascade / Basigin interactions / cyclosporin A binding / Minus-strand DNA synthesis / Plus-strand DNA synthesis / Uncoating of the HIV Virion / Early Phase of HIV Life Cycle / Integration of provirus / APOBEC3G mediated resistance to HIV-1 infection / viral release from host cell / Calcineurin activates NFAT / protein peptidyl-prolyl isomerization / Binding and entry of HIV virion / positive regulation of viral genome replication / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / : / neutrophil chemotaxis / activation of protein kinase B activity / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / negative regulation of protein phosphorylation / platelet aggregation / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / positive regulation of protein secretion / negative regulation of protein kinase activity / Assembly Of The HIV Virion / Budding and maturation of HIV virion / neuron differentiation / platelet activation / SARS-CoV-1 activates/modulates innate immune responses / unfolded protein binding / integrin binding / Platelet degranulation / protein folding / positive regulation of NF-kappaB transcription factor activity / cellular response to oxidative stress / secretory granule lumen / vesicle / ficolin-1-rich granule lumen / positive regulation of MAPK cascade / positive regulation of protein phosphorylation / focal adhesion / Neutrophil degranulation / apoptotic process / protein-containing complex / RNA binding / extracellular space / extracellular exosome / extracellular region / membrane / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / Resolution: 2.301 Å | ||||||
Authors | Appleby, T.C. / Steadman, V. / Pettit, S. / Schmitz, U. / Mackman, R.L. / Schultz, B. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Discovery of Potent Cyclophilin Inhibitors Based on the Structural Simplification of Sanglifehrin A. Authors: Steadman, V.A. / Pettit, S.B. / Poullennec, K.G. / Lazarides, L. / Keats, A.J. / Dean, D.K. / Stanway, S.J. / Austin, C.A. / Sanvoisin, J.A. / Watt, G.M. / Fliri, H.G. / Liclican, A.C. / ...Authors: Steadman, V.A. / Pettit, S.B. / Poullennec, K.G. / Lazarides, L. / Keats, A.J. / Dean, D.K. / Stanway, S.J. / Austin, C.A. / Sanvoisin, J.A. / Watt, G.M. / Fliri, H.G. / Liclican, A.C. / Jin, D. / Wong, M.H. / Leavitt, S.A. / Lee, Y.J. / Tian, Y. / Frey, C.R. / Appleby, T.C. / Schmitz, U. / Jansa, P. / Mackman, R.L. / Schultz, B.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5t9u.cif.gz | 154.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5t9u.ent.gz | 122.7 KB | Display | PDB format |
PDBx/mmJSON format | 5t9u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5t9u_validation.pdf.gz | 2.1 MB | Display | wwPDB validaton report |
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Full document | 5t9u_full_validation.pdf.gz | 2.1 MB | Display | |
Data in XML | 5t9u_validation.xml.gz | 33.6 KB | Display | |
Data in CIF | 5t9u_validation.cif.gz | 47.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t9/5t9u ftp://data.pdbj.org/pub/pdb/validation_reports/t9/5t9u | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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3 |
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4 |
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Unit cell |
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-Components
#1: Protein | Mass: 17907.389 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PPIA, CYPA / Production host: Escherichia coli (E. coli) / References: UniProt: P62937, peptidylprolyl isomerase #2: Chemical | ChemComp-7HG / Type: peptide-like, Peptide-like / Class: Inhibitor / Mass: 642.783 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C34H50N4O8 References: 3-[(3-hydroxyphenyl)methyl]-10,12-dimethoxy-9,11-dimethyl-6-(propan-2-yl)-19-oxa-1,4,7,25-tetraazabicyclo[19.3.1]pentacosa-13,15-diene-2,5,8,20-tetrone #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: 4.83 Å3/Da / Density % sol: 74.51 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 8.5 Details: 0.1 M Tris-HCl, pH 8.5 0.1 M potassium chloride 2.2 M ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Mar 7, 2011 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.5→45.162 Å / Num. obs: 61531 / % possible obs: 99.9 % / Redundancy: 4.49 % / Rmerge(I) obs: 0.043 / Net I/σ(I): 20.7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Resolution: 2.301→45.162 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 19.43
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 93.79 Å2 / Biso mean: 31.7922 Å2 / Biso min: 14.13 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.301→45.162 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: 14
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