[English] 日本語
Yorodumi
- PDB-2f6z: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2f6z
TitleProtein tyrosine phosphatase 1B with sulfamic acid inhibitors
ComponentsTyrosine-protein phosphatase, non-receptor type 1
KeywordsHYDROLASE / PTP1B / sulfamic acids / tetrahydroisoquinoline / phosphatase / tyrosine
Function / homology
Function and homology information


regulation of hepatocyte growth factor receptor signaling pathway / PTK6 Down-Regulation / positive regulation of receptor catabolic process / insulin receptor recycling / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / negative regulation of vascular endothelial growth factor receptor signaling pathway / negative regulation of PERK-mediated unfolded protein response / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / cytoplasmic side of endoplasmic reticulum membrane ...regulation of hepatocyte growth factor receptor signaling pathway / PTK6 Down-Regulation / positive regulation of receptor catabolic process / insulin receptor recycling / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / negative regulation of vascular endothelial growth factor receptor signaling pathway / negative regulation of PERK-mediated unfolded protein response / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / cytoplasmic side of endoplasmic reticulum membrane / platelet-derived growth factor receptor-beta signaling pathway / sorting endosome / mitochondrial crista / positive regulation of IRE1-mediated unfolded protein response / regulation of type I interferon-mediated signaling pathway / regulation of endocytosis / non-membrane spanning protein tyrosine phosphatase activity / positive regulation of protein tyrosine kinase activity / peptidyl-tyrosine dephosphorylation / Regulation of IFNA/IFNB signaling / regulation of signal transduction / cellular response to unfolded protein / growth hormone receptor signaling pathway via JAK-STAT / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / negative regulation of signal transduction / Regulation of IFNG signaling / MECP2 regulates neuronal receptors and channels / Growth hormone receptor signaling / endoplasmic reticulum unfolded protein response / positive regulation of JUN kinase activity / negative regulation of insulin receptor signaling pathway / Insulin receptor recycling / ephrin receptor binding / Integrin signaling / protein dephosphorylation / protein-tyrosine-phosphatase / negative regulation of MAP kinase activity / protein phosphatase 2A binding / protein tyrosine phosphatase activity / endosome lumen / insulin receptor binding / Negative regulation of MET activity / negative regulation of ERK1 and ERK2 cascade / receptor tyrosine kinase binding / insulin receptor signaling pathway / actin cytoskeleton organization / early endosome / mitochondrial matrix / cadherin binding / protein kinase binding / enzyme binding / endoplasmic reticulum / protein-containing complex / RNA binding / zinc ion binding / cytosol / cytoplasm
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 / Tyrosine specific protein phosphatases domain profile. / Protein-tyrosine phosphatase-like / Alpha-Beta Complex / Alpha Beta
Similarity search - Domain/homology
Chem-UN5 / Tyrosine-protein phosphatase non-receptor type 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å
AuthorsEvdokimov, A.G. / Pokross, M.E. / Klopfenstein, S.R.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2006
Title: 1,2,3,4-Tetrahydroisoquinolinyl sulfamic acids as phosphatase PTP1B inhibitors
Authors: Klopfenstein, S.R. / Evdokimov, A.G. / Colson, A.-O. / Fairweather, N.T. / Neuman, J.J. / Maier, M.B. / Gray, J.L. / Gerwe, G.S. / Stake, G.E. / Howard, B.W. / Farmer, J.A. / Pokross, M.E. / ...Authors: Klopfenstein, S.R. / Evdokimov, A.G. / Colson, A.-O. / Fairweather, N.T. / Neuman, J.J. / Maier, M.B. / Gray, J.L. / Gerwe, G.S. / Stake, G.E. / Howard, B.W. / Farmer, J.A. / Pokross, M.E. / Downs, T.R. / Kasibhatla, B. / Peters, K.G.
History
DepositionNov 29, 2005Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 13, 2005Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.3Aug 23, 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 / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_symmetry / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_symmetry / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_symmetry / _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 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,3997
Polymers34,7211
Non-polymers6796
Water6,179343
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)87.996, 87.996, 104.656
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number152
Space group name H-MP3121

-
Components

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


Mass: 34720.566 Da / Num. of mol.: 1 / Fragment: Catalytic domain, residues 1-298
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN1, PTP1B / Plasmid: pET28a / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P18031, protein-tyrosine-phosphatase
#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#3: Chemical
ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-UN5 / {3(S)-METHYLCARBAMOYL-2-[3-(3-SULFOAMINO-PHENYL)-PROPIONYL]-1,2,3,4-TETRAHYDRO-ISOQUINOLIN-7-YL}-SULFAMIC ACID


Mass: 512.557 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H24N4O8S2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 343 / 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: 3.37 Å3/Da / Density % sol: 63.46 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 8
Details: 18% PEG4000, 200 mM MgCl2, 100 mM TRIS-HCl, pH 8.0, VAPOR DIFFUSION, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: May 5, 2001
RadiationMonochromator: SILICON / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.7→28 Å / Num. all: 51974 / Num. obs: 51974 / % possible obs: 99.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 4.6 % / Biso Wilson estimate: 24.9 Å2 / Rmerge(I) obs: 0.024 / Net I/σ(I): 23.8
Reflection shellResolution: 1.7→1.8 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.24 / Mean I/σ(I) obs: 4.55 / Num. unique all: 8129 / % possible all: 99.8

-
Processing

Software
NameVersionClassificationNB
REFMACrefinement
PDB_EXTRACT1.701data extraction
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1PTV

1ptv


Resolution: 1.7→28 Å / Cor.coef. Fo:Fc: 0.971 / Cor.coef. Fo:Fc free: 0.967 / SU B: 2.526 / SU ML: 0.045 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / ESU R: 0.077 / ESU R Free: 0.074 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.177 2651 5.1 %RANDOM
Rwork0.16 ---
all0.161 51974 --
obs0.161 51974 99.88 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 26.97 Å2
Baniso -1Baniso -2Baniso -3
1-0.18 Å20.09 Å20 Å2
2--0.18 Å20 Å2
3----0.27 Å2
Refinement stepCycle: LAST / Resolution: 1.7→28 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2427 0 39 343 2809
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0222650
X-RAY DIFFRACTIONr_angle_refined_deg1.9511.9733606
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2475335
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.03924.436133
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.35415501
X-RAY DIFFRACTIONr_dihedral_angle_4_deg23.4211518
X-RAY DIFFRACTIONr_chiral_restr0.1340.2383
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.022033
X-RAY DIFFRACTIONr_nbd_refined0.2230.21259
X-RAY DIFFRACTIONr_nbtor_refined0.320.21826
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1810.2260
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2090.231
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2560.215
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined0.1120.21
X-RAY DIFFRACTIONr_mcbond_it1.3091.51594
X-RAY DIFFRACTIONr_mcangle_it1.97922539
X-RAY DIFFRACTIONr_scbond_it3.22331193
X-RAY DIFFRACTIONr_scangle_it54.51049
LS refinement shellResolution: 1.7→1.744 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.238 175 -
Rwork0.21 3619 -
obs-3794 99.66 %
Refinement TLS params.Method: refined / Origin x: 43.75 Å / Origin y: 16.8815 Å / Origin z: 2.0646 Å
111213212223313233
T0.0057 Å2-0.0325 Å20.0298 Å2--0.1036 Å2-0.012 Å2---0.0665 Å2
L0.7622 °2-0.0154 °20.404 °2-0.7112 °2-0.0304 °2--1.1615 °2
S0.0274 Å °-0.027 Å °-0.0396 Å °0.018 Å °-0.0003 Å °-0.0359 Å °-0.0387 Å °-0.1079 Å °-0.0271 Å °
Refinement TLS groupSelection: ALL

+
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://pdbjlc1.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