[English] 日本語
Yorodumi
- PDB-1ph0: Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the S... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1ph0
TitleNon-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site
ComponentsProtein-tyrosine phosphatase, non-receptor type 1
KeywordsHYDROLASE / Protein Tyrosine Phosphatase 1B / oxalyl-aryl-benzoic acid compound inhibitor / salicylic acid moiety at the second site
Function / homology
Function and homology information


PTK6 Down-Regulation / regulation of hepatocyte growth factor receptor signaling pathway / positive regulation of receptor catabolic process / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / insulin receptor recycling / negative regulation of vascular endothelial growth factor receptor signaling pathway / negative regulation of PERK-mediated unfolded protein response / IRE1-mediated unfolded protein response / regulation of intracellular protein transport / cytoplasmic side of endoplasmic reticulum membrane ...PTK6 Down-Regulation / regulation of hepatocyte growth factor receptor signaling pathway / positive regulation of receptor catabolic process / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / insulin receptor recycling / negative regulation of vascular endothelial growth factor receptor signaling pathway / negative regulation of PERK-mediated unfolded protein response / IRE1-mediated unfolded protein response / regulation of intracellular protein transport / cytoplasmic side of endoplasmic reticulum membrane / sorting endosome / mitochondrial crista / platelet-derived growth factor receptor-beta signaling pathway / positive regulation of IRE1-mediated unfolded protein response / regulation of type I interferon-mediated signaling pathway / regulation of endocytosis / positive regulation of protein tyrosine kinase activity / non-membrane spanning protein tyrosine phosphatase 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 / Growth hormone receptor signaling / MECP2 regulates neuronal receptors and channels / negative regulation of MAP kinase activity / endoplasmic reticulum unfolded protein response / positive regulation of JUN kinase activity / negative regulation of insulin receptor signaling pathway / Insulin receptor recycling / ephrin receptor binding / protein dephosphorylation / Integrin signaling / protein-tyrosine-phosphatase / protein tyrosine phosphatase activity / protein phosphatase 2A binding / endosome lumen / insulin receptor binding / Negative regulation of MET activity / receptor tyrosine kinase binding / negative regulation of ERK1 and ERK2 cascade / 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-418 / Tyrosine-protein phosphatase non-receptor type 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsLiu, G. / Xin, Z. / Liang, H. / Abad-Zapatero, C. / Hajduk, P. / Janowick, D. / Szczepankiewicz, B. / Pei, Z. / Hutchins, C.W. / Ballaron, S.J.
CitationJournal: J.Med.Chem. / Year: 2003
Title: Selective Protein Tyrosine Phosphatase 1B Inhibitors: Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands.
Authors: Liu, G. / Xin, Z. / Liang, H. / Abad-Zapatero, C. / Hajduk, P.J. / Janowick, D.A. / Szczepankiewicz, B.G. / Pei, Z. / Hutchins, C.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T.H. / Berg, C. ...Authors: Liu, G. / Xin, Z. / Liang, H. / Abad-Zapatero, C. / Hajduk, P.J. / Janowick, D.A. / Szczepankiewicz, B.G. / Pei, Z. / Hutchins, C.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T.H. / Berg, C.E. / Rondinone, C.M. / Trevillyan, J.M. / Jirousek, M.R.
History
DepositionMay 29, 2003Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 29, 2003Provider: repository / Type: Initial release
Revision 1.1Apr 29, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Oct 11, 2017Group: Refinement description / Category: software / Item: _software.classification / _software.name
Revision 1.4Aug 16, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / entity / pdbx_entity_nonpoly / pdbx_initial_refinement_model / struct_site
Item: _chem_comp.name / _database_2.pdbx_DOI ..._chem_comp.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Remark 600HETEROGEN CARBONS BEYOND THE O23 ATOM WERE NOT SEEN IN THE ELECTRON DENSITY FOR THE 418 LIGAND.

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Protein-tyrosine phosphatase, non-receptor type 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0432
Polymers37,3661
Non-polymers6781
Water3,837213
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)88.940, 88.940, 105.363
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number152
Space group name H-MP3121

-
Components

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


Mass: 37365.637 Da / Num. of mol.: 1 / Fragment: PTP1B Catalytic domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN1 OR PTP1B / Plasmid: pT7-7 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(D33)pTPASE 1B / References: UniProt: P18031, protein-tyrosine-phosphatase
#2: Chemical ChemComp-418 / 2-{4-[2-(S)-ALLYLOXYCARBONYLAMINO-3-{4-[(2-CARBOXY-PHENYL)-OXALYL-AMINO]-PHENYL}-PROPIONYLAMINO]-BUTOXY}-6-HYDROXY-BENZ OIC ACID METHYL ESTER / COMPOUND 6 / N-(ALLYLOXYCARBONYL)-4-[N-(CARBOXY-FORMYL)-2-(BENZOIC ACID)-AMINO]-L-PHENYLALANINYL-AMINO-BUTYLOXY-(6-HYDROXY-BENZOIC ACID METHYL ESTER)


Mass: 677.655 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H35N3O12
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 213 / 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: 3.22 Å3/Da / Density % sol: 61.77 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.1
Details: Precipiation buffer: 100 mM Hepes, 0.2 M Magnesium Acetate, 14% v/v PEG8000, pH 7.1, VAPOR DIFFUSION, HANGING DROP, temperature 277K
Crystal grow
*PLUS
Method: unknown
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-ID
13-4 mg/mlprotein11
22-4 mMdithiothreitol11

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.5418 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Feb 2, 2001 / Details: mirrors
RadiationMonochromator: mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.2→20 Å / Num. all: 24002 / Num. obs: 22263 / % possible obs: 96.3 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 1 / Redundancy: 4.41 % / Biso Wilson estimate: 32.4 Å2 / Rmerge(I) obs: 0.08 / Rsym value: 0.08 / Net I/σ(I): 20.9
Reflection shellResolution: 2.2→2.28 Å / Redundancy: 4.1 % / Rmerge(I) obs: 0.375 / Mean I/σ(I) obs: 2.1 / Num. unique all: 1852 / Rsym value: 0.375 / % possible all: 75.4

-
Processing

Software
NameVersionClassification
CNX2000refinement
MAR345data collection
HKL-2000data scaling
CNX2000phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1PTY and internal refinement of other PTP1B:ligand complexes

1pty


Resolution: 2.2→19.8 Å / Rfactor Rfree error: 0.005 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / σ(I): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.227 1932 10 %RANDOM
Rwork0.192 ---
obs0.213 19340 77.5 %-
all-22229 --
Solvent computationSolvent model: FLAT MODEL / Bsol: 42.3748 Å2 / ksol: 0.345481 e/Å3
Displacement parametersBiso mean: 35.1 Å2
Baniso -1Baniso -2Baniso -3
1-2.3 Å26.49 Å20 Å2
2--2.3 Å20 Å2
3----4.61 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.3 Å0.24 Å
Luzzati d res low-6 Å
Luzzati sigma a0.25 Å0.22 Å
Refinement stepCycle: LAST / Resolution: 2.2→19.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2301 0 46 213 2560
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.007
X-RAY DIFFRACTIONc_angle_deg1.3
X-RAY DIFFRACTIONc_dihedral_angle_d22.3
X-RAY DIFFRACTIONc_improper_angle_d0.73
X-RAY DIFFRACTIONc_mcbond_it2.481.5
X-RAY DIFFRACTIONc_mcangle_it3.932
X-RAY DIFFRACTIONc_scbond_it3.952
X-RAY DIFFRACTIONc_scangle_it5.922.5
LS refinement shellResolution: 2.2→2.28 Å / Rfactor Rfree error: 0.027 / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.253 87 8.7 %
Rwork0.234 911 -
obs-1852 40.6 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.PARAMPROTEIN.TOP
X-RAY DIFFRACTION2WATER_REP.PARAM418.TOP
X-RAY DIFFRACTION3ION.PARAM
X-RAY DIFFRACTION4418.PAR
Refine LS restraints
*PLUS
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_dihedral_angle_d
X-RAY DIFFRACTIONc_dihedral_angle_deg22.3
X-RAY DIFFRACTIONc_improper_angle_d
X-RAY DIFFRACTIONc_improper_angle_deg0.73

+
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