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- PDB-1pyn: DUAL-SITE POTENT, SELECTIVE PROTEIN TYROSINE PHOSPHATASE 1B INHIB... -
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Open data
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Basic information
Entry | Database: PDB / ID: 1pyn | ||||||
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Title | DUAL-SITE POTENT, SELECTIVE PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR USING A LINKED FRAGMENT STRATEGY AND A MALONATE HEAD ON THE FIRST SITE | ||||||
![]() | Protein-tyrosine phosphatase, non-receptor type 1 | ||||||
![]() | HYDROLASE / PROTEIN TYROSINE PHOSPHATASE INHIBITED WITH DUAL SITE / MALONATE-CONTAINING INHIBITOR | ||||||
Function / homology | ![]() 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 | ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Zhonghua, P. / Lubben, T. / Trevillyan, J.M. / Stashko, M. / Ballaron, S.J. / Liang, H. | ||||||
![]() | ![]() Title: Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors. Authors: Pei, Z. / Li, X. / Liu, G. / Abad-Zapatero, C. / Lubben, T. / Zhang, T. / Ballaron, S.J. / Hutchins, C.W. / Trevillyan, J.M. / Jirousek, M.R. #1: ![]() Title: Discovery of a 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.H. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, ...Authors: Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T.H. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C.W. / Fesik, S.W. / Jirousek, M.R. #2: ![]() 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. #3: ![]() 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. #4: ![]() Title: Selective Protein Tyrosine Phosphatase 1B Inhibitors: Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands Authors: Liu, G. / Xin, Z. / Liang, H. / Abad-Zapatero, C. / Hajduk, P.J. / Janowick, D.A. / Szczepankiewicz, B.G. / Pei, Z. / Hutchins, C.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T.H. / Berg, C. ...Authors: Liu, G. / Xin, Z. / Liang, H. / Abad-Zapatero, C. / Hajduk, P.J. / Janowick, D.A. / Szczepankiewicz, B.G. / Pei, Z. / Hutchins, C.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T.H. / Berg, C.E. / Rondinone, C.M. / Trevillyan, J.M. / Jirousek, M.R. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 78.9 KB | Display | ![]() |
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PDB format | ![]() | 57.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 464.2 KB | Display | ![]() |
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Full document | ![]() | 468.7 KB | Display | |
Data in XML | ![]() | 8 KB | Display | |
Data in CIF | ![]() | 12.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 1tyrS S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() |
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#2: Chemical | ChemComp-941 / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.18 Å3/Da / Density % sol: 61.38 % |
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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 Magnesisum Acetate, 14% PEG8000, pH 7.10, VAPOR DIFFUSION, HANGING DROP, temperature 277K |
Crystal grow | *PLUS Method: unknown / Details: Barford, D., (1994) J. Mol. Biol., 239, 726. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() |
Detector | Type: MARRESEARCH / Detector: CCD / Date: May 9, 2001 / 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: 2.1→20 Å / Num. all: 26734 / Num. obs: 25276 / % possible obs: 94 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 1 / Redundancy: 4.5 % / Biso Wilson estimate: 29.4 Å2 / Rmerge(I) obs: 0.057 / Rsym value: 0.057 / Net I/σ(I): 20.2 |
Reflection shell | Resolution: 2.1→2.18 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.338 / Mean I/σ(I) obs: 2.23 / Num. unique all: 2784 / Rsym value: 0.338 / % possible all: 73 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB ENTRY 1TYR AND INITIAL INTERNAL REFINEMENT OF OTHER COMPLEXES. RESIDUE CYS215, LISTED IN REMARK 500, CORRESPONDS TO THE ACTIVE SITE CYS WHICH IS KNOWN TO BE IN A STRAINED ...Starting model: PDB ENTRY 1TYR AND INITIAL INTERNAL REFINEMENT OF OTHER COMPLEXES. 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. Resolution: 2.2→19.74 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
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 42.7672 Å2 / ksol: 0.353933 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 32.1 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.2→19.74 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.2→2.28 Å / Rfactor Rfree error: 0.025 / Total num. of bins used: 10
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Xplor file |
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