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- PDB-8exk: Crystal structure of PTP1B D181A/Q262A phosphatase domain with JA... -

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Basic information

Entry
Database: PDB / ID: 8exk
TitleCrystal structure of PTP1B D181A/Q262A phosphatase domain with JAK2 activation loop phosphopeptide
Components
  • Tyrosine-protein kinase JAK2 activation loop peptide
  • Tyrosine-protein phosphatase non-receptor type 1
KeywordsSIGNALING PROTEIN / PTP1B / JAK/STAT / IRK
Function / homology
Function and homology information


interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid signaling pathway / histone H3Y41 kinase activity / symbiont-induced defense-related programmed cell death / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / mammary gland epithelium development / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway ...interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid signaling pathway / histone H3Y41 kinase activity / symbiont-induced defense-related programmed cell death / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / mammary gland epithelium development / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / thrombopoietin-mediated signaling pathway / Signaling by Erythropoietin / collagen-activated signaling pathway / interleukin-12 receptor binding / Erythropoietin activates STAT5 / interleukin-5-mediated signaling pathway / activation of Janus kinase activity / response to interleukin-12 / Erythropoietin activates Phospholipase C gamma (PLCG) / positive regulation of leukocyte proliferation / type 1 angiotensin receptor binding / post-embryonic hemopoiesis / interleukin-12 receptor complex / erythropoietin-mediated signaling pathway / interleukin-23 receptor complex / interleukin-23-mediated signaling pathway / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / interleukin-12-mediated signaling pathway / positive regulation of MHC class II biosynthetic process / positive regulation of NK T cell proliferation / acetylcholine receptor binding / positive regulation of platelet activation / cellular response to interleukin-3 / interleukin-3-mediated signaling pathway / positive regulation of platelet aggregation / Signaling by Leptin / Interleukin-12 signaling / positive regulation of epithelial cell apoptotic process / IL-6-type cytokine receptor ligand interactions / Interleukin-27 signaling / Interleukin-35 Signalling / regulation of nitric oxide biosynthetic process / growth hormone receptor binding / positive regulation of cell-substrate adhesion / axon regeneration / response to hydroperoxide / extrinsic component of cytoplasmic side of plasma membrane / regulation of receptor signaling pathway via JAK-STAT / negative regulation of cardiac muscle cell apoptotic process / growth hormone receptor signaling pathway / intrinsic apoptotic signaling pathway in response to oxidative stress / positive regulation of tyrosine phosphorylation of STAT protein / PTK6 Down-Regulation / negative regulation of cell-cell adhesion / regulation of hepatocyte growth factor receptor signaling pathway / extrinsic component of plasma membrane / positive regulation of receptor catabolic process / Interleukin-20 family signaling / insulin receptor recycling / IFNG signaling activates MAPKs / Interleukin-6 signaling / negative regulation of vascular endothelial growth factor receptor signaling pathway / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / peptide hormone receptor binding / enzyme-linked receptor protein signaling pathway / interleukin-6-mediated signaling pathway / positive regulation of protein tyrosine kinase activity / MAPK3 (ERK1) activation / response to amine / Prolactin receptor signaling / 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 / MAPK1 (ERK2) activation / platelet-derived growth factor receptor signaling pathway / positive regulation of JUN kinase activity / mesoderm development / positive regulation of systemic arterial blood pressure / negative regulation of MAP kinase activity / positive regulation of interleukin-17 production / positive regulation of natural killer cell proliferation / vascular endothelial cell response to oscillatory fluid shear stress / regulation of endocytosis / response to tumor necrosis factor / peptidyl-tyrosine dephosphorylation / non-membrane spanning protein tyrosine phosphatase activity / Regulation of IFNA/IFNB signaling / signaling receptor activator activity / regulation of proteolysis / cellular response to angiotensin / Interleukin-3, Interleukin-5 and GM-CSF signaling / positive regulation of SMAD protein signal transduction
Similarity search - Function
Tyrosine-protein kinase, non-receptor Jak2 / Janus kinase 2, pseudokinase domain / Janus kinase 2, catalytic domain / Tyrosine-protein kinase JAK2, SH2 domain / JAK2, FERM domain C-lobe / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : ...Tyrosine-protein kinase, non-receptor Jak2 / Janus kinase 2, pseudokinase domain / Janus kinase 2, catalytic domain / Tyrosine-protein kinase JAK2, SH2 domain / JAK2, FERM domain C-lobe / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : / Jak1 pleckstrin homology-like domain / FERM F2 acyl-CoA binding protein-like domain / FERM F1 ubiquitin-like domain / SH2 domain / Protein-tyrosine phosphatase, non-receptor type-1/2 / : / FERM central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / 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 / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
PHOSPHATE ION / Tyrosine-protein kinase JAK2 / Tyrosine-protein phosphatase non-receptor type 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.096 Å
AuthorsMorris, R. / Kershaw, N.J. / Babon, J.J.
Funding support Australia, 1items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia) Australia
CitationJournal: Commun Biol / Year: 2023
Title: Structure guided studies of the interaction between PTP1B and JAK.
Authors: Morris, R. / Keating, N. / Tan, C. / Chen, H. / Laktyushin, A. / Saiyed, T. / Liau, N.P.D. / Nicola, N.A. / Tiganis, T. / Kershaw, N.J. / Babon, J.J.
History
DepositionOct 25, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 5, 2023Provider: repository / Type: Initial release
Revision 1.1Oct 25, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Tyrosine-protein phosphatase non-receptor type 1
B: Tyrosine-protein kinase JAK2 activation loop peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,4923
Polymers36,3982
Non-polymers951
Water1,892105
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area890 Å2
ΔGint-9 kcal/mol
Surface area13260 Å2
MethodPISA
Unit cell
Length a, b, c (Å)88.493, 88.493, 130.411
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212

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Components

#1: Protein Tyrosine-protein phosphatase non-receptor type 1 / Protein-tyrosine phosphatase 1B / PTP-1B


Mass: 34472.359 Da / Num. of mol.: 1 / Mutation: D181A/Q262A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN1, PTP1B / Production host: Escherichia coli (E. coli) / References: UniProt: P18031, protein-tyrosine-phosphatase
#2: Protein/peptide Tyrosine-protein kinase JAK2 activation loop peptide / Janus kinase 2 / JAK-2


Mass: 1925.161 Da / Num. of mol.: 1 / Fragment: residues 1000-1015 of JAK2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
References: UniProt: O60674, non-specific protein-tyrosine kinase
#3: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 105 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

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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: 3.63 Å3/Da / Density % sol: 66.14 %
Crystal growTemperature: 281.15 K / Method: vapor diffusion, hanging drop / Details: 14% PEG 8K, 0.10 M Mg Acetate, 0.1 M MES (pH 6.5)

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.95373 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 27, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95373 Å / Relative weight: 1
ReflectionResolution: 2.09→45.148 Å / Num. obs: 31017 / % possible obs: 99.54 % / Redundancy: 7.4 % / CC1/2: 0.999 / Net I/σ(I): 21.46
Reflection shellResolution: 2.09→2.17 Å / Num. unique obs: 1743 / CC1/2: 0.11

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Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1PTY

1pty


Resolution: 2.096→45.148 Å / SU ML: 0.35 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 30.09 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2502 2611 8.44 %
Rwork0.2159 28343 -
obs0.2188 30954 99.55 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 100.45 Å2 / Biso mean: 54.6596 Å2 / Biso min: 32.04 Å2
Refinement stepCycle: final / Resolution: 2.096→45.148 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2409 0 5 105 2519
Biso mean--52.93 53.47 -
Num. residues----302
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.0963-2.13440.44861240.4039133992
2.1344-2.17550.34371360.33631479100
2.1755-2.21990.33481340.30581471100
2.2199-2.26820.36961350.28271457100
2.2682-2.32090.32471380.2781481100
2.3209-2.3790.36341350.28121464100
2.379-2.44330.28561340.2741481100
2.4433-2.51520.36361370.27791472100
2.5152-2.59630.33761350.27561475100
2.5963-2.68910.33641380.27841488100
2.6891-2.79680.29751350.25291477100
2.7968-2.92410.29151390.2551505100
2.9241-3.07820.2561370.25111484100
3.0782-3.2710.26931380.23191504100
3.271-3.52340.24991400.2281512100
3.5234-3.87790.23431390.19041515100
3.8779-4.43860.19721400.16931527100
4.4386-5.59050.19891440.16611552100
5.5905-45.1480.20661530.18531660100

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