[English] 日本語
Yorodumi
- PDB-6ol2: Crystallography of novel WNK1 and WNK3 inhibitors discovered from... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ol2
TitleCrystallography of novel WNK1 and WNK3 inhibitors discovered from high-throughput-screening
ComponentsSerine/threonine-protein kinase WNK1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


negative regulation of cell-cell adhesion mediated by integrin / lymphocyte migration into lymph node / chemokine (C-C motif) ligand 21 signaling pathway / monoatomic cation homeostasis / positive regulation of termination of RNA polymerase II transcription / negative regulation of pancreatic juice secretion / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / monoatomic ion homeostasis / positive regulation of mitotic cytokinesis / negative regulation of sodium ion transport ...negative regulation of cell-cell adhesion mediated by integrin / lymphocyte migration into lymph node / chemokine (C-C motif) ligand 21 signaling pathway / monoatomic cation homeostasis / positive regulation of termination of RNA polymerase II transcription / negative regulation of pancreatic juice secretion / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / monoatomic ion homeostasis / positive regulation of mitotic cytokinesis / negative regulation of sodium ion transport / positive regulation of potassium ion import across plasma membrane / regulation of mRNA export from nucleus / intracellular chloride ion homeostasis / negative regulation of heterotypic cell-cell adhesion / positive regulation of T cell chemotaxis / regulation of sodium ion transmembrane transport / potassium channel inhibitor activity / cellular response to chemokine / potassium ion homeostasis / negative regulation of leukocyte cell-cell adhesion / cellular hyperosmotic response / membraneless organelle assembly / cell volume homeostasis / regulation of monoatomic cation transmembrane transport / protein serine/threonine kinase inhibitor activity / intracellular membraneless organelle / positive regulation of systemic arterial blood pressure / protein kinase activator activity / negative regulation of protein localization to plasma membrane / phosphatase binding / regulation of sodium ion transport / monoatomic ion transport / negative regulation of protein ubiquitination / sodium ion transmembrane transport / negative regulation of autophagy / cellular response to calcium ion / GABA-ergic synapse / modulation of chemical synaptic transmission / molecular condensate scaffold activity / regulation of blood pressure / positive regulation of angiogenesis / mitotic spindle / positive regulation of canonical Wnt signaling pathway / T cell receptor signaling pathway / heart development / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / protein kinase binding / magnesium ion binding / signal transduction / protein-containing complex / ATP binding / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
: / Serine/threonine-protein kinase OSR1/WNK, CCT domain / Oxidative-stress-responsive kinase 1 C-terminal domain / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain ...: / Serine/threonine-protein kinase OSR1/WNK, CCT domain / Oxidative-stress-responsive kinase 1 C-terminal domain / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
ACETATE ION / Chem-MU7 / Serine/threonine-protein kinase WNK1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsChlebowicz, J. / Akella, R. / Sekulski, K. / Humphreys, J.M. / Durbacz, M.Z. / He, H. / Rodan, A. / Posner, B. / Goldsmith, E.J.
Funding support United States, 1items
OrganizationGrant numberCountry
American Heart Association16SA285300002 United States
CitationJournal: To Be Published
Title: Crystallography of novel WNK1 and WNK3 inhibitors discovered from high throughput screening
Authors: Chlebowicz, J. / Akella, R. / Sekulski, K. / Humphreys, J.M. / Durbacz, M.Z. / He, H. / Rodan, A. / Posner, B. / Goldsmith, E.J.
History
DepositionApr 15, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 15, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase WNK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5059
Polymers33,4811
Non-polymers1,0248
Water3,567198
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1170 Å2
ΔGint-2 kcal/mol
Surface area14900 Å2
MethodPISA
Unit cell
Length a, b, c (Å)38.925, 60.204, 65.502
Angle α, β, γ (deg.)90.00, 93.05, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Serine/threonine-protein kinase WNK1 / Protein kinase lysine-deficient 1 / Protein kinase with no lysine 1


Mass: 33481.496 Da / Num. of mol.: 1 / Fragment: UNP residues 194-483 / Mutation: S382A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Wnk1, Hsn2, Prkwnk1 / Plasmid: pHis / Production host: Escherichia coli (E. coli)
References: UniProt: Q9JIH7, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-MU7 / N-[2-(5,8-dimethoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]-2-iodobenzamide


Mass: 478.280 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H19IN2O4
#3: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H3O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 198 / 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: 2.4 Å3/Da / Density % sol: 48.75 % / Description: Plates
Crystal growTemperature: 289 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 20% PEG3350, 0.2 M sodium formate

-
Data collection

DiffractionMean temperature: 80 K / Ambient temp details: liquid nitrogen / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97905 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Mar 18, 2018
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97905 Å / Relative weight: 1
ReflectionResolution: 2.1→50 Å / Num. obs: 18499 / % possible obs: 94.6 % / Redundancy: 3.4 % / Rsym value: 0.08 / Net I/σ(I): 24.1
Reflection shellHighest resolution: 2.1 Å / Redundancy: 2.4 % / Num. unique obs: 600 / Rsym value: 0.541 / % possible all: 94

-
Processing

Software
NameVersionClassification
REFMAC5.8.0238refinement
HKL-3000data reduction
HKL-3000data scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 5DRB

5drb


Resolution: 2.1→34.25 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.879 / SU B: 11.202 / SU ML: 0.154 / Cross valid method: THROUGHOUT / ESU R: 0.305 / ESU R Free: 0.238 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflectionSelection details
Rfree0.26754 811 5 %RANDOM
Rwork0.20209 ---
obs0.20528 15346 90.74 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 28.844 Å2
Baniso -1Baniso -2Baniso -3
1--0.04 Å20 Å20.09 Å2
2--0.04 Å2-0 Å2
3----0.01 Å2
Refinement stepCycle: 1 / Resolution: 2.1→34.25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2236 0 63 198 2497
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0230.0122336
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg0.5811.6623132
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.6735278
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.04321.88117
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.51415437
X-RAY DIFFRACTIONr_dihedral_angle_4_deg25.5981516
X-RAY DIFFRACTIONr_chiral_restr0.0590.2300
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.021730
X-RAY DIFFRACTIONr_gen_planes_other
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_it3.4831.6781119
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it4.7272.481392
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it5.52.1611217
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined10.14823.9053703
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.1→2.154 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.299 45 -
Rwork0.204 953 -
obs--75.32 %
Refinement TLS params.Method: refined / Origin x: 4.5044 Å / Origin y: -0.448 Å / Origin z: 15.9866 Å
111213212223313233
T0.0826 Å20.0035 Å20.0059 Å2-0.1193 Å20.0083 Å2--0.0068 Å2
L0.4507 °20.0019 °2-0.259 °2-0.419 °2-0.3259 °2--0.7639 °2
S0.0082 Å °0.1991 Å °-0.0123 Å °0.1059 Å °-0.0745 Å °-0.0264 Å °0.0532 Å °0.0076 Å °0.0663 Å °

+
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