[English] 日本語
Yorodumi
- PDB-5ehp: Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Al... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ehp
TitleNon-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor SHP836
ComponentsTyrosine-protein phosphatase non-receptor type 11
KeywordsHydrolase/Hydrolase Inhibitor / Phosphatase PTP Inhibitor PTPN11 Allosteric / Hydrolase-Hydrolase Inhibitor complex
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 / Netrin mediated repulsion signals / positive regulation of hormone secretion ...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 / Netrin mediated repulsion signals / positive regulation of hormone secretion / cerebellar cortex formation / multicellular organismal reproductive process / regulation of protein export from nucleus / positive regulation of ossification / hormone metabolic process / Interleukin-37 signaling / Signaling by Leptin / negative regulation of chondrocyte differentiation / MET activates PTPN11 / Regulation of RUNX1 Expression and Activity / face morphogenesis / ERBB signaling pathway / Costimulation by the CD28 family / Signal regulatory protein family interactions / peptide hormone receptor binding / negative regulation of type I interferon production / platelet formation / megakaryocyte development / organ growth / triglyceride metabolic process / CTLA4 inhibitory signaling / Platelet sensitization by LDL / Interleukin-20 family signaling / PI-3K cascade:FGFR3 / Interleukin-6 signaling / STAT5 activation downstream of FLT3 ITD mutants / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR4 / Prolactin receptor signaling / PI-3K cascade:FGFR1 / MAPK3 (ERK1) activation / MAPK1 (ERK2) activation / PECAM1 interactions / phosphoprotein phosphatase activity / Bergmann glial cell differentiation / regulation of cell adhesion mediated by integrin / regulation of type I interferon-mediated signaling pathway / neurotrophin TRK receptor signaling pathway / inner ear development / platelet-derived growth factor receptor signaling pathway / non-membrane spanning protein tyrosine phosphatase activity / RET signaling / peptidyl-tyrosine dephosphorylation / Interleukin-3, Interleukin-5 and GM-CSF signaling / PI3K Cascade / Regulation of IFNA/IFNB signaling / PD-1 signaling / negative regulation of insulin secretion / regulation of protein-containing complex assembly / ephrin receptor signaling pathway / fibroblast growth factor receptor signaling pathway / GAB1 signalosome / Activated NTRK2 signals through FRS2 and FRS3 / Regulation of IFNG signaling / positive regulation of insulin receptor signaling pathway / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / homeostasis of number of cells within a tissue / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / FRS-mediated FGFR1 signaling / GPVI-mediated activation cascade / cell adhesion molecule binding / cellular response to epidermal growth factor stimulus / Tie2 Signaling / T cell costimulation / FLT3 Signaling / positive regulation of interferon-beta production / hormone-mediated signaling pathway / phosphotyrosine residue binding / positive regulation of mitotic cell cycle / Downstream signal transduction / axonogenesis / protein dephosphorylation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / protein tyrosine kinase binding / protein-tyrosine-phosphatase / DNA damage checkpoint signaling / protein tyrosine phosphatase activity / integrin-mediated signaling pathway / positive regulation of glucose import / Negative regulation of FGFR3 signaling / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / Negative regulation of FGFR1 signaling / Spry regulation of FGF signaling / brain development / insulin receptor binding / epidermal growth factor receptor signaling pathway
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
Chem-5OA / PHOSPHATE ION / Tyrosine-protein phosphatase non-receptor type 11
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.85 Å
AuthorsStams, T. / Fodor, M.
CitationJournal: J.Med.Chem. / Year: 2016
Title: Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor.
Authors: Garcia Fortanet, J. / Chen, C.H. / Chen, Y.N. / Chen, Z. / Deng, Z. / Firestone, B. / Fekkes, P. / Fodor, M. / Fortin, P.D. / Fridrich, C. / Grunenfelder, D. / Ho, S. / Kang, Z.B. / Karki, R. ...Authors: Garcia Fortanet, J. / Chen, C.H. / Chen, Y.N. / Chen, Z. / Deng, Z. / Firestone, B. / Fekkes, P. / Fodor, M. / Fortin, P.D. / Fridrich, C. / Grunenfelder, D. / Ho, S. / Kang, Z.B. / Karki, R. / Kato, M. / Keen, N. / LaBonte, L.R. / Larrow, J. / Lenoir, F. / Liu, G. / Liu, S. / Lombardo, F. / Majumdar, D. / Meyer, M.J. / Palermo, M. / Perez, L. / Pu, M. / Ramsey, T. / Sellers, W.R. / Shultz, M.D. / Stams, T. / Towler, C. / Wang, P. / Williams, S.L. / Zhang, J.H. / LaMarche, M.J.
History
DepositionOct 28, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 6, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 21, 2016Group: Database references
Revision 1.2Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)122,13412
Polymers120,6702
Non-polymers1,46410
Water11,764653
1
A: Tyrosine-protein phosphatase non-receptor type 11
hetero molecules


Theoretical massNumber of molelcules
Total (without water)61,1627
Polymers60,3351
Non-polymers8276
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein phosphatase non-receptor type 11
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,9725
Polymers60,3351
Non-polymers6374
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)46.310, 213.730, 55.980
Angle α, β, γ (deg.)90.000, 96.820, 90.000
Int Tables number4
Space group name H-MP1211

-
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: 60335.035 Da / Num. of mol.: 2 / Fragment: UNP residues 1-525
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN11, PTP2C, SHPTP2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q06124, protein-tyrosine-phosphatase
#2: Chemical ChemComp-5OA / 5-[2,3-bis(chloranyl)phenyl]-2-[(3~{R},5~{S})-3,5-dimethylpiperazin-1-yl]pyrimidin-4-amine / SHP836


Mass: 352.262 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H19Cl2N5
#3: Chemical
ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: PO4
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 653 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.28 Å3/Da / Density % sol: 46.04 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / Details: 17% PEG 3350, 200mM Ammonium Phosphate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 22, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.85→200 Å / Num. obs: 87497 / % possible obs: 95.9 % / Redundancy: 3.2 % / Rmerge(I) obs: 0.044 / Net I/σ(I): 15.9
Reflection shellResolution: 1.85→1.95 Å / Redundancy: 2.4 % / Rmerge(I) obs: 0.362 / Mean I/σ(I) obs: 2.1 / % possible all: 76.4

-
Processing

Software
NameVersionClassification
XSCALEdata scaling
BUSTERBUSTER 2.11.5refinement
PDB_EXTRACT3.15data extraction
XDSdata reduction
BUSTERphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: 2SHP

2shp


Resolution: 1.85→27.09 Å / Cor.coef. Fo:Fc: 0.9525 / Cor.coef. Fo:Fc free: 0.9375 / SU R Cruickshank DPI: 0.132 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.132 / SU Rfree Blow DPI: 0.122 / SU Rfree Cruickshank DPI: 0.122
RfactorNum. reflection% reflectionSelection details
Rfree0.2084 4388 5.02 %RANDOM
Rwork0.1745 ---
obs0.1762 87407 95.5 %-
Displacement parametersBiso max: 111.88 Å2 / Biso mean: 34.24 Å2 / Biso min: 12.78 Å2
Baniso -1Baniso -2Baniso -3
1--4.8841 Å20 Å21.8716 Å2
2--2.0054 Å20 Å2
3---2.8787 Å2
Refine analyzeLuzzati coordinate error obs: 0.195 Å
Refinement stepCycle: final / Resolution: 1.85→27.09 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7825 0 86 654 8565
Biso mean--49.56 39.27 -
Num. residues----965
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d2891SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes219HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1155HARMONIC5
X-RAY DIFFRACTIONt_it8104HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1015SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact9607SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d8104HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg10940HARMONIC21
X-RAY DIFFRACTIONt_omega_torsion3.32
X-RAY DIFFRACTIONt_other_torsion18.13
LS refinement shellResolution: 1.85→1.9 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2643 257 5.65 %
Rwork0.2225 4290 -
all0.2248 4547 -
obs--95.5 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more