[English] 日本語
Yorodumi
- PDB-3o5x: Crystal structure of the oncogenic tyrosine phosphatase SHP2 comp... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3o5x
TitleCrystal structure of the oncogenic tyrosine phosphatase SHP2 complexed with a salicylic acid-based small molecule inhibitor
ComponentsTyrosine-protein phosphatase non-receptor type 11
KeywordsHYDROLASE / SHP2-IIB-08 complex / inhibitor / binding affinity / binding selectivity / receptor / Dephosphorylation
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 / negative regulation of chondrocyte differentiation / Signaling by Leptin / 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 / triglyceride metabolic process / platelet formation / negative regulation of type I interferon production / megakaryocyte development / organ growth / 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 / phosphoprotein phosphatase activity / inner ear development / MAPK1 (ERK2) activation / PECAM1 interactions / Bergmann glial cell differentiation / regulation of cell adhesion mediated by integrin / neurotrophin TRK receptor signaling pathway / regulation of type I interferon-mediated signaling pathway / 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 / ephrin receptor signaling pathway / regulation of protein-containing complex assembly / 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 / homeostasis of number of cells within a tissue / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / cellular response to epidermal growth factor stimulus / FRS-mediated FGFR1 signaling / GPVI-mediated activation cascade / Tie2 Signaling / protein tyrosine kinase binding / T cell costimulation / FLT3 Signaling / positive regulation of interferon-beta production / hormone-mediated signaling pathway / cell adhesion molecule binding / phosphotyrosine residue binding / positive regulation of mitotic cell cycle / axonogenesis / Downstream signal transduction / protein dephosphorylation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / protein-tyrosine-phosphatase / DNA damage checkpoint signaling / protein tyrosine phosphatase activity / integrin-mediated signaling pathway / Negative regulation of FGFR3 signaling / Negative regulation of FGFR2 signaling / positive regulation of glucose import / Negative regulation of FGFR4 signaling / Negative regulation of FGFR1 signaling / brain development / Spry regulation of FGF signaling / multicellular organism growth / insulin receptor binding
Similarity search - Function
Protein-tyrosine phosphatase, non-receptor type-6, -11 / 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, non-receptor type-6, -11 / 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 / Alpha Beta
Similarity search - Domain/homology
Chem-JZG / Tyrosine-protein phosphatase non-receptor type 11
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsZhang, Z.-Y. / Zhang, X. / He, Y. / Liu, S. / Yu, Z. / Jiang, Z. / Yang, Z. / Dong, Y. / Nabinger, S.C. / Wu, L. ...Zhang, Z.-Y. / Zhang, X. / He, Y. / Liu, S. / Yu, Z. / Jiang, Z. / Yang, Z. / Dong, Y. / Nabinger, S.C. / Wu, L. / Gunawan, A.M. / Wang, L. / Chan, R.J.
CitationJournal: J.Med.Chem. / Year: 2010
Title: Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2).
Authors: Zhang, X. / He, Y. / Liu, S. / Yu, Z. / Jiang, Z.X. / Yang, Z. / Dong, Y. / Nabinger, S.C. / Wu, L. / Gunawan, A.M. / Wang, L. / Chan, R.J. / Zhang, Z.Y.
History
DepositionJul 28, 2010Deposition site: RCSB / Processing site: RCSB
SupersessionAug 11, 2010ID: 3JRL
Revision 1.0Aug 11, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Sep 6, 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 / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)32,8352
Polymers32,2781
Non-polymers5581
Water2,414134
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)39.544, 75.829, 48.214
Angle α, β, γ (deg.)90.00, 98.53, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 32277.703 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 262-532, CATALYTIC DOMAIN / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q06124, protein-tyrosine-phosphatase
#2: Chemical ChemComp-JZG / 3-{1-[3-(biphenyl-4-ylamino)-3-oxopropyl]-1H-1,2,3-triazol-4-yl}-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid


Mass: 557.599 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C33H27N5O4
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 134 / 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: 2.21 Å3/Da / Density % sol: 44.46 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 20%PEG3350,1%v/v Tacsimate pH7.0, 100mM NaCl, 100 mM HEPES, pH7.5 , VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-BM
DetectorDate: Mar 1, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 1.66→50 Å / Num. obs: 27801 / % possible obs: 83 %

-
Processing

Software
NameVersionClassification
AMoREphasing
CNS1.1refinement
HKL-3000data reduction
HKL-3000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3B7O

3b7o


Resolution: 2→50 Å / σ(F): 2 / Stereochemistry target values: Engh & Huber
RfactorNum. reflectionSelection details
Rfree0.238 903 RANDOM
Rwork0.1961 --
all-19089 -
obs-18964 -
Refinement stepCycle: LAST / Resolution: 2→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2074 0 42 134 2250
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.0067
X-RAY DIFFRACTIONc_angle_deg1.23

+
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