+Open data
-Basic information
Entry | Database: PDB / ID: 1ony | ||||||
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Title | Oxalyl-Aryl-Amino Benzoic Acid inhibitors of PTP1B, compound 17 | ||||||
Components | Protein-tyrosine phosphatase, non-receptor type 1 | ||||||
Keywords | HYDROLASE / Protein Tyrosine Phosphatase / oxalyl-aryl-amino benzoic acid inhibitor | ||||||
Function / homology | Function and homology information regulation of hepatocyte growth factor receptor signaling pathway / PTK6 Down-Regulation / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / positive regulation of receptor catabolic process / insulin receptor recycling / negative regulation of PERK-mediated unfolded protein response / negative regulation of vascular endothelial growth factor receptor signaling pathway / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / cytoplasmic side of endoplasmic reticulum membrane ...regulation of hepatocyte growth factor receptor signaling pathway / PTK6 Down-Regulation / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / positive regulation of receptor catabolic process / insulin receptor recycling / negative regulation of PERK-mediated unfolded protein response / negative regulation of vascular endothelial growth factor receptor signaling pathway / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / cytoplasmic side of endoplasmic reticulum membrane / platelet-derived growth factor receptor-beta signaling pathway / sorting endosome / mitochondrial crista / positive regulation of IRE1-mediated unfolded protein response / regulation of type I interferon-mediated signaling pathway / regulation of endocytosis / non-membrane spanning protein tyrosine phosphatase activity / positive regulation of protein tyrosine kinase activity / peptidyl-tyrosine dephosphorylation / Regulation of IFNA/IFNB signaling / regulation of signal transduction / cellular response to unfolded protein / growth hormone receptor signaling pathway via JAK-STAT / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / negative regulation of signal transduction / Regulation of IFNG signaling / Growth hormone receptor signaling / MECP2 regulates neuronal receptors and channels / endoplasmic reticulum unfolded protein response / positive regulation of JUN kinase activity / Insulin receptor recycling / negative regulation of insulin receptor signaling pathway / ephrin receptor binding / Integrin signaling / protein dephosphorylation / protein-tyrosine-phosphatase / negative regulation of MAP kinase activity / protein phosphatase 2A binding / protein tyrosine phosphatase activity / endosome lumen / insulin receptor binding / Negative regulation of MET activity / negative regulation of ERK1 and ERK2 cascade / receptor tyrosine kinase binding / insulin receptor signaling pathway / actin cytoskeleton organization / early endosome / mitochondrial matrix / cadherin binding / protein kinase binding / enzyme binding / endoplasmic reticulum / protein-containing complex / RNA binding / zinc ion binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.15 Å | ||||||
Authors | Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. ...Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T. / Mika, A.K. / Zinker, B.A. / Trevillyan, J.M. / Jirousek, M.R. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2003 Title: Discovery and Structure-Activity Relationship of Oxalylarylaminobenzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B Authors: Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, ...Authors: Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T. / Mika, A.K. / Zinker, B.A. / Trevillyan, J.M. / Jirousek, M.R. #1: Journal: BIOORG.MED.CHEM.LETT. / Year: 2003 Title: Potent, Selective Inhibitors of Protein Tyrosine Phosphatase 1B Authors: Xin, Z. / Oost, T.K. / Abad-Zapatero, C. / Hajduk, P.J. / Pei, Z. / Szczepankiewicz, B.G. / Hutchins, C.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T. / Trevillyan, J.M. / Jirousek, M.R. / Liu, G. #2: Journal: J.Am.Chem.Soc. / Year: 2003 Title: Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Strategy Authors: Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C. ...Authors: Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C.W. / Fesik, S.W. / Jirousek, M.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1ony.cif.gz | 79.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1ony.ent.gz | 58.4 KB | Display | PDB format |
PDBx/mmJSON format | 1ony.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1ony_validation.pdf.gz | 470.6 KB | Display | wwPDB validaton report |
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Full document | 1ony_full_validation.pdf.gz | 475.7 KB | Display | |
Data in XML | 1ony_validation.xml.gz | 8.4 KB | Display | |
Data in CIF | 1ony_validation.cif.gz | 13.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/on/1ony ftp://data.pdbj.org/pub/pdb/validation_reports/on/1ony | HTTPS FTP |
-Related structure data
Related structure data | 1onzC 1tyrS 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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Unit cell |
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-Components
#1: Protein | Mass: 37365.637 Da / Num. of mol.: 1 / Fragment: PTP1B Catalytic domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN1 OR PTP1B / Plasmid: pT7-7 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(D33)/pTPASE 1B / References: UniProt: P18031, protein-tyrosine-phosphatase |
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#2: Chemical | ChemComp-588 / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.22 Å3/Da / Density % sol: 61.83 % | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.1 Details: Precipitation buffer: 100 mM Hepes, 0.2 M Magnesium Acetate, 14% PEG8000, pH 7.1, VAPOR DIFFUSION, HANGING DROP, temperature 277K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS Temperature: 4 ℃ / pH: 7.5 Details: Puius, Y.A., (1997) Proc.Natl.Acad.Sci.USA, 94, 13420. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RU300 / Wavelength: 1.5418 Å |
Detector | Type: MARRESEARCH / Detector: CCD / Date: Aug 1, 2000 / Details: mirrors |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2→50 Å / Num. all: 32536 / Num. obs: 30332 / % possible obs: 81.3 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 1 / Redundancy: 4.8 % / Biso Wilson estimate: 33.3 Å2 / Rmerge(I) obs: 0.065 / Rsym value: 0.065 / Net I/σ(I): 16.9 |
Reflection shell | Resolution: 2→2.07 Å / Redundancy: 4.1 % / Rmerge(I) obs: 0.571 / Mean I/σ(I) obs: 2.1 / Num. unique all: 3152 / Rsym value: 0.571 / % possible all: 96.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1TYR and initial internal refinement Resolution: 2.15→17.44 Å / Rfactor Rfree error: 0.005 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / σ(I): 0 / Stereochemistry target values: Engh & Huber Details: Residue CYS215, listed in remark 500, corresponds to the active site CYS which is known to be in a strained conformation in this class of enzymes. Strained conformation of Gly259 is caused ...Details: Residue CYS215, listed in remark 500, corresponds to the active site CYS which is known to be in a strained conformation in this class of enzymes. Strained conformation of Gly259 is caused by the presence of the inhibitor in the active site and in the vicinity of Gln262.
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 73.0446 Å2 / ksol: 0.388378 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 36.2 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.15→17.44 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.15→2.23 Å / Rfactor Rfree error: 0.017 / Total num. of bins used: 10
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Xplor file |
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Refinement | *PLUS Rfactor Rfree: 0.22 | ||||||||||||||||||||||||||||||||||||
Solvent computation | *PLUS | ||||||||||||||||||||||||||||||||||||
Displacement parameters | *PLUS | ||||||||||||||||||||||||||||||||||||
Refine LS restraints | *PLUS
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