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- PDB-5bk8: Cancer-associated SHP2/T507K mutant -

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Basic information

Entry
Database: PDB / ID: 5bk8
TitleCancer-associated SHP2/T507K mutant
ComponentsTyrosine-protein phosphatase non-receptor type 11
KeywordsHYDROLASE / Phosphatase / SHP2 / PTPN11 / T507K
Function / homology
Function and homology information


negative regulation of cortisol secretion / intestinal epithelial cell migration / microvillus organization / negative regulation of growth hormone secretion / genitalia development / atrioventricular canal development / negative regulation of cell adhesion mediated by integrin / STAT5 Activation / Co-inhibition by BTLA / Netrin mediated repulsion signals ...negative regulation of cortisol secretion / intestinal epithelial cell migration / microvillus organization / negative regulation of growth hormone secretion / genitalia development / atrioventricular canal development / negative regulation of cell adhesion mediated by integrin / STAT5 Activation / Co-inhibition by BTLA / Netrin mediated repulsion signals / cerebellar cortex formation / negative regulation of neutrophil activation / positive regulation of hormone secretion / regulation of protein export from nucleus / positive regulation of ossification / positive regulation of lipopolysaccharide-mediated signaling pathway / Interleukin-37 signaling / Signaling by Leptin / hormone metabolic process / MET activates PTPN11 / Regulation of RUNX1 Expression and Activity / negative regulation of chondrocyte differentiation / face morphogenesis / Signal regulatory protein family interactions / ERBB signaling pathway / platelet formation / Interleukin-20 family signaling / Interleukin-6 signaling / triglyceride metabolic process / organ growth / megakaryocyte development / peptide hormone receptor binding / negative regulation of type I interferon production / PI-3K cascade:FGFR3 / Co-inhibition by CTLA4 / MAPK3 (ERK1) activation / Platelet sensitization by LDL / STAT5 activation downstream of FLT3 ITD mutants / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR4 / PI-3K cascade:FGFR1 / MAPK1 (ERK2) activation / Prolactin receptor signaling / regulation of cell adhesion mediated by integrin / regulation of type I interferon-mediated signaling pathway / PECAM1 interactions / inner ear development / neurotrophin TRK receptor signaling pathway / Bergmann glial cell differentiation / Regulation of IFNA/IFNB signaling / positive regulation of intracellular signal transduction / peptidyl-tyrosine dephosphorylation / platelet-derived growth factor receptor signaling pathway / phosphoprotein phosphatase activity / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / PI3K Cascade / ephrin receptor signaling pathway / Co-inhibition by PD-1 / fibroblast growth factor receptor signaling pathway / GAB1 signalosome / regulation of protein-containing complex assembly / Activated NTRK2 signals through FRS2 and FRS3 / positive regulation of insulin receptor signaling pathway / Regulation of IFNG signaling / negative regulation of insulin secretion / Signaling by CSF3 (G-CSF) / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / GPVI-mediated activation cascade / cell adhesion molecule binding / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Tie2 Signaling / FRS-mediated FGFR1 signaling / homeostasis of number of cells within a tissue / hormone-mediated signaling pathway / negative regulation of T cell proliferation / T cell costimulation / FLT3 Signaling / phosphotyrosine residue binding / protein tyrosine phosphatase activity / protein-tyrosine-phosphatase / protein tyrosine phosphatase activity, metal-dependent / histone H2AXY142 phosphatase activity / non-membrane spanning protein tyrosine phosphatase activity / Downstream signal transduction / positive regulation of mitotic cell cycle / cellular response to epidermal growth factor stimulus / axonogenesis / positive regulation of interferon-beta production / protein tyrosine kinase binding / DNA damage checkpoint signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / integrin-mediated signaling pathway / positive regulation of D-glucose import / Negative regulation of FGFR3 signaling / insulin receptor binding / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling
Similarity search - Function
Protein-tyrosine phosphatase, non-receptor type-6, -11 / SH2 domain / SHC Adaptor Protein / 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, non-receptor type-6, -11 / SH2 domain / SHC Adaptor Protein / 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 / Tyrosine specific protein phosphatases domain profile. / Protein-tyrosine phosphatase-like / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Alpha-Beta Complex / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Tyrosine-protein phosphatase non-receptor type 11
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.25 Å
AuthorsYu, Z.H. / Zhang, R.Y. / Zhang, Z.Y.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)RO1 CA69202 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)RO1 CA207288 United States
CitationJournal: J.Biol.Chem. / Year: 2020
Title: Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2.
Authors: Zhang, R.Y. / Yu, Z.H. / Chen, L. / Walls, C.D. / Zhang, S. / Wu, L. / Zhang, Z.Y.
History
DepositionJun 1, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 8, 2020Provider: repository / Type: Initial release
Revision 1.1May 13, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.2Sep 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Tyrosine-protein phosphatase non-receptor type 11


Theoretical massNumber of molelcules
Total (without water)61,7901
Polymers61,7901
Non-polymers00
Water4,161231
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area22690 Å2
Unit cell
Length a, b, c (Å)54.699, 203.176, 44.366
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212

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Components

#1: Protein Tyrosine-protein phosphatase non-receptor type 11 / Protein-tyrosine phosphatase 1D / PTP-1D / Protein-tyrosine phosphatase 2C / PTP-2C / SH-PTP2 / Shp2 / SH-PTP3


Mass: 61789.719 Da / Num. of mol.: 1 / Mutation: T507K
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN11, PTP2C, SHPTP2
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: Q06124, protein-tyrosine-phosphatase
#2: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 231 / 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: 1.99 Å3/Da / Density % sol: 38.34 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 16% PEG3350, 200 mM LiCl

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97857 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 1, 2011
Diffraction measurementDetails: 1.00 degrees, 11.0 sec, detector distance 327.42 mm
Method: \w scans
RadiationMonochromator: SI(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionAv R equivalents: 0.14 / Number: 105858
ReflectionResolution: 2.25→50 Å / Num. obs: 23674 / % possible obs: 95.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 4.5 % / Rmerge(I) obs: 0.14 / Rsym value: 0.14 / Net I/av σ(I): 12.744 / Net I/σ(I): 12.66 / Num. measured all: 105858
Reflection shellResolution: 2.25→2.29 Å / Redundancy: 4 % / Rmerge(I) obs: 0.811 / Mean I/σ(I) obs: 1.487 / Num. unique obs: 1139 / Rsym value: 0.811 / % possible all: 93.8
Cell measurementReflection used: 105858

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Processing

Software
NameVersionClassification
HKL-3000data reduction
SCALEPACKdata scaling
PHENIX1.10.1_2155refinement
PDB_EXTRACT3.25data extraction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4DGP

4dgp


Resolution: 2.25→40.658 Å / SU ML: 0.3 / Cross valid method: THROUGHOUT / σ(F): 1.44 / Phase error: 25.69
RfactorNum. reflection% reflection
Rfree0.262 1168 5.01 %
Rwork0.1982 --
obs0.2014 23297 95.44 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 90.43 Å2 / Biso mean: 31.3359 Å2 / Biso min: 10.66 Å2
Refinement stepCycle: final / Resolution: 2.25→40.658 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4028 0 0 231 4259
Biso mean---32.35 -
Num. residues----498
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0084111
X-RAY DIFFRACTIONf_angle_d1.0055540
X-RAY DIFFRACTIONf_chiral_restr0.056594
X-RAY DIFFRACTIONf_plane_restr0.006718
X-RAY DIFFRACTIONf_dihedral_angle_d15.682469
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 8

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.25-2.35240.33351430.24472654279792
2.3524-2.47640.32081470.2282737288497
2.4764-2.63150.31091440.23042731287597
2.6315-2.83470.32361450.22082755290097
2.8347-3.11980.28441430.21612760290396
3.1198-3.57110.2641480.19032751289995
3.5711-4.49820.23281410.16542780292194
4.4982-40.66440.20931570.18632961311896

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