[English] 日本語
Yorodumi
- PDB-1nl9: Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1nl9
TitlePotent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 12 Using a Linked-Fragment Strategy
ComponentsProtein-tyrosine phosphatase, non-receptor type 1
KeywordsHYDROLASE / Protein Tyrosine Phosphatase fold / Dual-site Oxamic Acid Inhibitor bound to P-loop
Function / homology
Function and homology information


regulation of hepatocyte growth factor receptor signaling pathway / cytoplasmic side of endoplasmic reticulum membrane / regulation of intracellular protein transport / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / positive regulation of receptor catabolic process / negative regulation of PERK-mediated unfolded protein response / mitochondrial crista / negative regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of IRE1-mediated unfolded protein response / platelet-derived growth factor receptor-beta signaling pathway ...regulation of hepatocyte growth factor receptor signaling pathway / cytoplasmic side of endoplasmic reticulum membrane / regulation of intracellular protein transport / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / positive regulation of receptor catabolic process / negative regulation of PERK-mediated unfolded protein response / mitochondrial crista / negative regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of IRE1-mediated unfolded protein response / platelet-derived growth factor receptor-beta signaling pathway / negative regulation of signal transduction / sorting endosome / regulation of type I interferon-mediated signaling pathway / regulation of signal transduction / regulation of endocytosis / IRE1-mediated unfolded protein response / growth hormone receptor signaling pathway via JAK-STAT / peptidyl-tyrosine dephosphorylation / negative regulation of insulin receptor signaling pathway / endoplasmic reticulum unfolded protein response / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / activation of JUN kinase activity / actin cytoskeleton reorganization / cellular response to unfolded protein / negative regulation of MAP kinase activity / protein phosphatase 2A binding / protein-tyrosine-phosphatase / negative regulation of ERK1 and ERK2 cascade / positive regulation of protein tyrosine kinase activity / protein dephosphorylation / protein tyrosine phosphatase activity / ephrin receptor binding / receptor tyrosine kinase binding / insulin receptor binding / insulin receptor signaling pathway / early endosome / mitochondrial matrix / cadherin binding / protein kinase binding / endoplasmic reticulum / enzyme binding / protein-containing complex / RNA binding / zinc ion binding / cytosol
Protein-tyrosine phosphatase-like / Protein-tyrosine phosphatase, active site / Protein-tyrosine phosphatase, non-receptor type-1/2 / Protein-tyrosine phosphatase, catalytic / Tyrosine specific protein phosphatases domain / PTP type protein phosphatase / Protein tyrosine phosphatase superfamily / Protein-Tyrosine Phosphatase; Chain A / Alpha-Beta Complex / Alpha Beta
Tyrosine-protein phosphatase non-receptor type 1
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsSzczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C.W. / Fesik, S.W. / Jirousek, M.R.
CitationJournal: J.Am.Chem.Soc. / Year: 2003
Title: Discovery of a Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Strategy
Authors: Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C. ...Authors: Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C.W. / Fesik, S.W. / Jirousek, M.R.
Validation Report
SummaryFull reportAbout validation report
History
DepositionJan 6, 2003Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 8, 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

-
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)37,8992
Polymers37,3661
Non-polymers5341
Water5,134285
1


TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
γ
α
β
Length a, b, c (Å)88.730, 88.730, 105.910
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 / 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-989 / 2-{[4-(2-ACETYLAMINO-2-PENTYLCARBAMOYL-ETHYL)-NAPHTHALEN-1-YL]-OXALYL-AMINO}-BENZOIC ACID / COMPOUND 12, N-ACETYL-4-[(CARBOXYCARBONYL)(2-CARBOXYPHENYL)AMINO]-N-PENTYL-1-NAPTHYLALANIAMIDE


Mass: 533.572 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C29H31N3O7
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 285 / 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: 61.79 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.1
Details: Precipitation buffer 100 mM Hepes, 0.2 M Magnesium Acetate, 14% 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 RU300 / Wavelength: 1.5418 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Jul 4, 2002 / 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: 2.3→50 Å / Num. all: 20366 / Num. obs: 19212 / % possible obs: 92.1 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 1 / Redundancy: 4.4 % / Biso Wilson estimate: 32.4 Å2 / Rmerge(I) obs: 0.07 / Rsym value: 0.07 / Net I/σ(I): 15.2
Reflection shellResolution: 2.4→2.49 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.258 / Mean I/σ(I) obs: 4.06 / Num. unique all: 1458 / Rsym value: 0.258 / % possible all: 77.5

-
Processing

Software
NameVersionClassification
CNX2000refinement
MAR345data collection
HKL-2000data scaling
CNX2000phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1TYR and initial internal refinement
Resolution: 2.4→19.77 Å / Rfactor Rfree error: 0.006 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / σ(I): 0 / Stereochemistry target values: Engh & Huber
Details: Residue CYS215, listed in remark 500, corresponds to the active site CYS which is known to be in a strained conformation in this class of enzymes.
RfactorNum. reflection% reflectionSelection details
Rfree0.247 1618 9.9 %RANDOM
Rwork0.192 ---
All0.262 18704 --
Obs0.208 16316 84.6 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 48.1088 Å2 / ksol: 0.343571 e/Å3
Displacement parametersBiso mean: 26.9 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.35 Å0.26 Å
Luzzati d res low-6 Å
Luzzati sigma a0.23 Å0.15 Å
Refinement stepCycle: LAST / Resolution: 2.4→19.77 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2301 0 39 285 2625
Refine LS restraints
Refinement-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.006
X-RAY DIFFRACTIONc_angle_deg1.2
X-RAY DIFFRACTIONc_dihedral_angle_d21.7
X-RAY DIFFRACTIONc_improper_angle_d0.7
X-RAY DIFFRACTIONc_mcbond_it2.021.5
X-RAY DIFFRACTIONc_mcangle_it3.212
X-RAY DIFFRACTIONc_scbond_it3.42
X-RAY DIFFRACTIONc_scangle_it5.122.5
LS refinement shellResolution: 2.4→2.49 Å / Rfactor Rfree error: 0.033 / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.344 110 10.6 %
Rwork0.259 924 -
Obs-1019 55.3 %
Xplor file
Refinement-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.PARAMPROTEIN.TOP
X-RAY DIFFRACTION2989.PAR989.TOP
Refinement
*PLUS
Solvent computation
*PLUS
Displacement parameters
*PLUS
Refine LS restraints
*PLUS
Refinement-IDTypeDev ideal
X-RAY DIFFRACTIONc_dihedral_angle_d
X-RAY DIFFRACTIONc_dihedral_angle_deg21.7
X-RAY DIFFRACTIONc_improper_angle_d
X-RAY DIFFRACTIONc_improper_angle_deg0.7

+
About Yorodumi

-
News

-
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices

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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.:Changes in new EM Navigator and Yorodumi

Read more

-
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.

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