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- PDB-2bge: Structure-based design of Protein Tyrosine Phosphatase-1B Inhibitors -

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Basic information

Entry
Database: PDB / ID: 2bge
TitleStructure-based design of Protein Tyrosine Phosphatase-1B Inhibitors
ComponentsPROTEIN-TYROSINE PHOSPHATASE NON-RECEPTOR TYPE 1
KeywordsHYDROLASE / PROTEIN TYROSINE PHOSPHATASE / 1 / 2 / 5-THIADIAZOLIDIN-3-ONE-1 / 1-DIOXIDE TEMPLATE
Function / homology
Function and homology information


PTK6 Down-Regulation / regulation of hepatocyte growth factor receptor signaling pathway / positive regulation of receptor catabolic process / insulin receptor recycling / negative regulation of vascular endothelial growth factor receptor signaling pathway / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / positive regulation of protein tyrosine kinase activity / platelet-derived growth factor receptor-beta signaling pathway / sorting endosome ...PTK6 Down-Regulation / regulation of hepatocyte growth factor receptor signaling pathway / positive regulation of receptor catabolic process / insulin receptor recycling / negative regulation of vascular endothelial growth factor receptor signaling pathway / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / positive regulation of protein tyrosine kinase activity / platelet-derived growth factor receptor-beta signaling pathway / sorting endosome / negative regulation of vascular associated smooth muscle cell migration / mitochondrial crista / cytoplasmic side of endoplasmic reticulum membrane / positive regulation of IRE1-mediated unfolded protein response / regulation of type I interferon-mediated signaling pathway / negative regulation of PERK-mediated unfolded protein response / positive regulation of JUN kinase activity / positive regulation of systemic arterial blood pressure / negative regulation of MAP kinase activity / vascular endothelial cell response to oscillatory fluid shear stress / regulation of endocytosis / peptidyl-tyrosine dephosphorylation / non-membrane spanning protein tyrosine phosphatase activity / Regulation of IFNA/IFNB signaling / regulation of proteolysis / cellular response to angiotensin / regulation of postsynapse assembly / positive regulation of endothelial cell apoptotic process / growth hormone receptor signaling pathway via JAK-STAT / negative regulation of cell-substrate adhesion / cellular response to unfolded protein / regulation of signal transduction / Regulation of IFNG signaling / negative regulation of signal transduction / Growth hormone receptor signaling / positive regulation of heart rate / positive regulation of cardiac muscle cell apoptotic process / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / protein dephosphorylation / endoplasmic reticulum unfolded protein response / MECP2 regulates neuronal receptors and channels / ephrin receptor binding / Insulin receptor recycling / cellular response to platelet-derived growth factor stimulus / cellular response to fibroblast growth factor stimulus / Integrin signaling / protein-tyrosine-phosphatase / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to nitric oxide / negative regulation of insulin receptor signaling pathway / protein tyrosine phosphatase activity / protein phosphatase 2A binding / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / endosome lumen / insulin receptor binding / response to nutrient levels / Negative regulation of MET activity / cellular response to nerve growth factor stimulus / receptor tyrosine kinase binding / negative regulation of ERK1 and ERK2 cascade / insulin receptor signaling pathway / negative regulation of neuron projection development / actin cytoskeleton organization / cellular response to hypoxia / early endosome / postsynapse / cadherin binding / mitochondrial matrix / negative regulation of cell population proliferation / protein kinase binding / glutamatergic synapse / enzyme binding / endoplasmic reticulum / protein-containing complex / RNA binding / zinc ion binding / cytoplasm / cytosol
Similarity search - Function
Protein-tyrosine phosphatase, non-receptor type-1/2 / : / Protein tyrosine phosphatase superfamily / Protein-Tyrosine Phosphatase; Chain A / Protein tyrosine phosphatase, catalytic domain / PTP type protein phosphatase domain profile. / Protein-tyrosine phosphatase / Tyrosine-specific protein phosphatase, PTPase domain / Protein-tyrosine phosphatase, catalytic / Protein tyrosine phosphatase, catalytic domain motif ...Protein-tyrosine phosphatase, non-receptor type-1/2 / : / Protein tyrosine phosphatase superfamily / Protein-Tyrosine Phosphatase; Chain A / Protein tyrosine phosphatase, catalytic domain / PTP type protein phosphatase domain profile. / Protein-tyrosine phosphatase / Tyrosine-specific protein phosphatase, PTPase domain / Protein-tyrosine phosphatase, catalytic / Protein tyrosine phosphatase, catalytic domain motif / Tyrosine specific protein phosphatases active site. / Protein-tyrosine phosphatase, active site / Tyrosine specific protein phosphatases domain profile. / Tyrosine-specific protein phosphatases domain / Protein-tyrosine phosphatase-like / Alpha-Beta Complex / Alpha Beta
Similarity search - Domain/homology
1,2,5-THIADIAZOLIDIN-3-ONE-1,1-DIOXIDE / Tyrosine-protein phosphatase non-receptor type 1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsBlack, E. / Breed, J. / Breeze, A.L. / Embrey, K. / Garcia, R. / Gero, T.W. / Godfrey, L. / Kenny, P.W. / Morley, A.D. / Minshull, C.A. ...Black, E. / Breed, J. / Breeze, A.L. / Embrey, K. / Garcia, R. / Gero, T.W. / Godfrey, L. / Kenny, P.W. / Morley, A.D. / Minshull, C.A. / Pannifer, A.D. / Read, J. / Rees, A. / Russell, D.J. / Toader, D. / Tucker, J.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2005
Title: Structure-Based Design of Protein Tyrosine Phosphatase-1B Inhibitors
Authors: Black, E. / Breed, J. / Breeze, A.L. / Embrey, K. / Garcia, R. / Gero, T.W. / Godfrey, L. / Kenny, P.W. / Morley, A.D. / Minshull, C.A. / Pannifer, A.D. / Read, J. / Rees, A. / Russell, D.J. ...Authors: Black, E. / Breed, J. / Breeze, A.L. / Embrey, K. / Garcia, R. / Gero, T.W. / Godfrey, L. / Kenny, P.W. / Morley, A.D. / Minshull, C.A. / Pannifer, A.D. / Read, J. / Rees, A. / Russell, D.J. / Toader, D. / Tucker, J.
History
DepositionDec 21, 2004Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 4, 2005Provider: repository / Type: Initial release
Revision 1.1Oct 7, 2015Group: Derived calculations / Non-polymer description ...Derived calculations / Non-polymer description / Other / Refinement description / Source and taxonomy / Version format compliance
Revision 1.2May 8, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: PROTEIN-TYROSINE PHOSPHATASE NON-RECEPTOR TYPE 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,5782
Polymers37,3661
Non-polymers2121
Water6,792377
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPQS
Unit cell
Length a, b, c (Å)89.012, 89.012, 104.710
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number152
Space group name H-MP3121

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Components

#1: Protein PROTEIN-TYROSINE PHOSPHATASE NON-RECEPTOR TYPE 1 / PROTEIN-TYROSINE PHOSPHATASE 1B / PTP-1B


Mass: 37365.637 Da / Num. of mol.: 1 / Fragment: PTP1B CATALYTIC DOMAIN, RESIDUES 1-321
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P18031, protein-tyrosine-phosphatase
#2: Chemical ChemComp-T2D / 1,2,5-THIADIAZOLIDIN-3-ONE-1,1-DIOXIDE


Mass: 212.226 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H8N2O3S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 377 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 3.2 Å3/Da / Density % sol: 54 %
Crystal growpH: 6.5 / Details: pH 6.50

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SRS / Beamline: PX9.6 / Wavelength: 0.96
DetectorType: ADSC CCD / Detector: CCD / Date: Dec 15, 2001
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.96 Å / Relative weight: 1
ReflectionResolution: 1.8→43.4 Å / Num. obs: 45256 / % possible obs: 99.7 % / Observed criterion σ(I): 2 / Redundancy: 3.6 % / Rmerge(I) obs: 0.07 / Net I/σ(I): 11
Reflection shellResolution: 1.8→1.97 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.42 / Mean I/σ(I) obs: 1.8 / % possible all: 99.2

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Processing

Software
NameVersionClassification
CNX2000refinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.8→43 Å / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2449 2247 5 %RANDOM
Rwork0.2183 ---
obs-44794 --
Solvent computationBsol: 34.8782 Å2 / ksol: 0.356412 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1--0.502 Å2-1.15 Å20 Å2
2---0.502 Å20 Å2
3---1.003 Å2
Refinement stepCycle: LAST / Resolution: 1.8→43 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2424 0 14 377 2815
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.009
X-RAY DIFFRACTIONc_bond_d_na
X-RAY DIFFRACTIONc_bond_d_prot
X-RAY DIFFRACTIONc_angle_d
X-RAY DIFFRACTIONc_angle_d_na
X-RAY DIFFRACTIONc_angle_d_prot
X-RAY DIFFRACTIONc_angle_deg1.2603
X-RAY DIFFRACTIONc_angle_deg_na
X-RAY DIFFRACTIONc_angle_deg_prot
X-RAY DIFFRACTIONc_dihedral_angle_d
X-RAY DIFFRACTIONc_dihedral_angle_d_na
X-RAY DIFFRACTIONc_dihedral_angle_d_prot
X-RAY DIFFRACTIONc_improper_angle_d
X-RAY DIFFRACTIONc_improper_angle_d_na
X-RAY DIFFRACTIONc_improper_angle_d_prot
X-RAY DIFFRACTIONc_mcbond_it
X-RAY DIFFRACTIONc_mcangle_it
X-RAY DIFFRACTIONc_scbond_it
X-RAY DIFFRACTIONc_scangle_it

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