[English] 日本語
Yorodumi
- PDB-8tk2: HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8tk2
TitleHUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed with 2-((2,4-difluorobenzyl)amino)-2-oxoacetic acid
ComponentsDual specificity protein phosphatase 3
KeywordsHYDROLASE / PROTEIN DUAL-SPECIFICITY PHOSPHATASE / VHR
Function / homology
Function and homology information


peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / MAP kinase phosphatase activity / protein tyrosine/serine/threonine phosphatase activity / negative regulation of chemotaxis / negative regulation of T cell activation / positive regulation of focal adhesion disassembly / ERKs are inactivated / negative regulation of JNK cascade / motile cilium / regulation of focal adhesion assembly ...peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / MAP kinase phosphatase activity / protein tyrosine/serine/threonine phosphatase activity / negative regulation of chemotaxis / negative regulation of T cell activation / positive regulation of focal adhesion disassembly / ERKs are inactivated / negative regulation of JNK cascade / motile cilium / regulation of focal adhesion assembly / dephosphorylation / negative regulation of T cell receptor signaling pathway / histone H2AXS140 phosphatase activity / RNA polymerase II CTD heptapeptide repeat Y1 phosphatase activity / RNA polymerase II CTD heptapeptide repeat T4 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MAP kinase serine/threonine phosphatase activity / calmodulin-dependent protein phosphatase activity / myosin phosphatase activity / protein-serine/threonine phosphatase / negative regulation of epidermal growth factor receptor signaling pathway / phosphatase activity / peptidyl-tyrosine dephosphorylation / immunological synapse / negative regulation of MAPK cascade / cytoskeletal protein binding / protein tyrosine phosphatase activity / protein-tyrosine-phosphatase / protein tyrosine phosphatase activity, metal-dependent / histone H2AXY142 phosphatase activity / non-membrane spanning protein tyrosine phosphatase activity / positive regulation of mitotic cell cycle / cellular response to epidermal growth factor stimulus / protein tyrosine kinase binding / negative regulation of cell migration / negative regulation of ERK1 and ERK2 cascade / receptor tyrosine kinase binding / cytoskeleton / protein kinase binding / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Atypical dual specificity phosphatase, subfamily A / Dual specificity phosphatase, catalytic domain / Dual specificity phosphatase, catalytic domain / Dual specificity phosphatase, catalytic domain / Dual specificity protein phosphatase domain profile. / Dual specificity protein phosphatase domain / 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
Similarity search - Domain/homology
: / DI(HYDROXYETHYL)ETHER / Dual specificity protein phosphatase 3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å
AuthorsAleshin, A.E. / Wu, J. / Lambert, L.J. / Cosford, N.D.P. / Tautz, L.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)1R21 AI160161 United States
CitationJournal: Acs Omega / Year: 2025
Title: Fragment Screening Identifies Novel Allosteric Binders and Binding Sites in the VHR ( DUSP3 ) Phosphatase.
Authors: Wu, J. / Baranowski, M.R. / Aleshin, A.E. / Isiorho, E.A. / Lambert, L.J. / De Backer, L.J.S. / Han, Y.N. / Das, R. / Sheffler, D.J. / Bobkov, A.A. / Lemberikman, A.M. / Keedy, D.A. / Cosford, N.D.P. / Tautz, L.
History
DepositionJul 25, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 14, 2024Provider: repository / Type: Initial release
Revision 1.1Feb 26, 2025Group: Database references / Structure summary / Category: citation / citation_author / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dual specificity protein phosphatase 3
B: Dual specificity protein phosphatase 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,1816
Polymers40,5662
Non-polymers6154
Water4,324240
1
A: Dual specificity protein phosphatase 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,4982
Polymers20,2831
Non-polymers2151
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Dual specificity protein phosphatase 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,6824
Polymers20,2831
Non-polymers3993
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)35.536, 44.328, 59.863
Angle α, β, γ (deg.)78.07, 89.99, 81.69
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein Dual specificity protein phosphatase 3 / Dual specificity protein phosphatase VHR / Vaccinia H1-related phosphatase / VHR


Mass: 20283.000 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DUSP3, VHR / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P51452, protein-serine/threonine phosphatase, protein-tyrosine-phosphatase
#2: Chemical ChemComp-I1Y / {[(2,4-difluorophenyl)methyl]amino}(oxo)acetic acid


Mass: 215.154 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C9H7F2NO3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 240 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.25 Å3/Da / Density % sol: 45.32 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop
Details: Protein-compound mixture in 50 mM TRIS-Cl pH 8.5, 1 mM TCEP, 0.5 mM EDTA, 5% DMSO were mixed with the precipitant solution (100 mM Bis-Tris pH 6.5, 50 mM NH4F, 28% (w/v) PEGME-2000) and ...Details: Protein-compound mixture in 50 mM TRIS-Cl pH 8.5, 1 mM TCEP, 0.5 mM EDTA, 5% DMSO were mixed with the precipitant solution (100 mM Bis-Tris pH 6.5, 50 mM NH4F, 28% (w/v) PEGME-2000) and equilibrated against the precipitant solution.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.97946 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 7, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 1.7→38.69 Å / Num. obs: 34755 / % possible obs: 89.4 % / Redundancy: 2 % / Rmerge(I) obs: 0.049 / Net I/σ(I): 8.8
Reflection shellResolution: 1.7→1.73 Å / Redundancy: 1.9 % / Rmerge(I) obs: 0.229 / Mean I/σ(I) obs: 2.7 / Num. unique obs: 1610 / % possible all: 80.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0411refinement
XDSdata reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.7→38.69 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.951 / SU B: 2.764 / SU ML: 0.088 / Cross valid method: THROUGHOUT / ESU R: 0.127 / ESU R Free: 0.126 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22265 2065 5.9 %RANDOM
Rwork0.17587 ---
obs0.1786 32683 89.31 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 29.235 Å2
Baniso -1Baniso -2Baniso -3
1-0.75 Å2-1.78 Å20.41 Å2
2--1.04 Å2-0.55 Å2
3----2.4 Å2
Refinement stepCycle: 1 / Resolution: 1.7→38.69 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2804 0 41 240 3085
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0123029
X-RAY DIFFRACTIONr_bond_other_d0.0010.0162874
X-RAY DIFFRACTIONr_angle_refined_deg1.431.6474110
X-RAY DIFFRACTIONr_angle_other_deg0.4861.5766616
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8025389
X-RAY DIFFRACTIONr_dihedral_angle_2_deg7.042520
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.50710530
X-RAY DIFFRACTIONr_dihedral_angle_4_deg
X-RAY DIFFRACTIONr_chiral_restr0.0730.2448
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.023716
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02720
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.7712.871517
X-RAY DIFFRACTIONr_mcbond_other2.7612.8711517
X-RAY DIFFRACTIONr_mcangle_it3.9815.1481919
X-RAY DIFFRACTIONr_mcangle_other3.9815.1511920
X-RAY DIFFRACTIONr_scbond_it3.5223.3091512
X-RAY DIFFRACTIONr_scbond_other3.5213.3111513
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other5.3275.8982192
X-RAY DIFFRACTIONr_long_range_B_refined6.89132.83479
X-RAY DIFFRACTIONr_long_range_B_other6.85931.753413
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.7→1.743 Å
RfactorNum. reflection% reflection
Rfree0.257 140 -
Rwork0.238 2207 -
obs--83.26 %

+
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