[English] 日本語
Yorodumi
- PDB-8enj: Design, synthesis, biological evaluation, and X-ray crystallograp... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8enj
TitleDesign, synthesis, biological evaluation, and X-ray crystallography of diarylpyrazole derivatives possessing terminal arylsulfonamide moieties as anti-proliferative agents targeting c-Jun N-terminal kinase (JNK)
ComponentsMitogen-activated protein kinase 10
KeywordsHYDROLASE / Cancer / JNK / Leukemia
Function / homology
Function and homology information


JUN kinase activity / Activation of the AP-1 family of transcription factors / Fc-epsilon receptor signaling pathway / MAP kinase kinase activity / response to light stimulus / mitogen-activated protein kinase / JNK cascade / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / FCERI mediated MAPK activation / regulation of circadian rhythm ...JUN kinase activity / Activation of the AP-1 family of transcription factors / Fc-epsilon receptor signaling pathway / MAP kinase kinase activity / response to light stimulus / mitogen-activated protein kinase / JNK cascade / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / FCERI mediated MAPK activation / regulation of circadian rhythm / cellular senescence / rhythmic process / Oxidative Stress Induced Senescence / protein phosphorylation / protein serine kinase activity / signal transduction / mitochondrion / nucleoplasm / ATP binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Mitogen-activated protein (MAP) kinase, JNK / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / 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
Similarity search - Domain/homology
Chem-WNK / Mitogen-activated protein kinase 10
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.81 Å
AuthorsPark, H. / Mersal, K.I.
Funding support Korea, Republic Of, 1items
OrganizationGrant numberCountry
National Research Foundation (NRF, Korea) Korea, Republic Of
CitationJournal: Eur.J.Med.Chem. / Year: 2023
Title: Evaluation of novel pyrazol-4-yl pyridine derivatives possessing arylsulfonamide tethers as c-Jun N-terminal kinase (JNK) inhibitors in leukemia cells.
Authors: Mersal, K.I. / Abdel-Maksoud, M.S. / Ali, E.M.H. / Ammar, U.M. / Zaraei, S.O. / Haque, M.M. / Das, T. / Hassan, N.F. / Kim, E.E. / Lee, J.S. / Park, H. / Lee, K.H. / El-Gamal, M.I. / Kim, H. ...Authors: Mersal, K.I. / Abdel-Maksoud, M.S. / Ali, E.M.H. / Ammar, U.M. / Zaraei, S.O. / Haque, M.M. / Das, T. / Hassan, N.F. / Kim, E.E. / Lee, J.S. / Park, H. / Lee, K.H. / El-Gamal, M.I. / Kim, H.K. / Ibrahim, T.M. / Oh, C.H.
History
DepositionSep 30, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 18, 2023Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mitogen-activated protein kinase 10
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,1712
Polymers52,6491
Non-polymers5221
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)51.670, 71.840, 107.230
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein Mitogen-activated protein kinase 10 / MAPK 10 / MAP kinase p49 3F12 / Stress-activated protein kinase 1b / SAPK1b / Stress-activated ...MAPK 10 / MAP kinase p49 3F12 / Stress-activated protein kinase 1b / SAPK1b / Stress-activated protein kinase JNK3 / c-Jun N-terminal kinase 3


Mass: 52649.332 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK10, JNK3, JNK3A, PRKM10, SAPK1B / Production host: Escherichia coli (E. coli)
References: UniProt: P53779, mitogen-activated protein kinase
#2: Chemical ChemComp-WNK / N-[3-({(4P)-4-[(3M)-1-tert-butyl-3-(3-hydroxyphenyl)-1H-pyrazol-4-yl]pyridin-2-yl}amino)propyl]-4-hydroxybenzene-1-sulfonamide


Mass: 521.631 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H31N5O4S / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

Crystal growTemperature: 277 K / Method: vapor diffusion / Details: 0.2 M ammonium tartrate pH 7.2, 18 % PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.999 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 28, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.999 Å / Relative weight: 1
ReflectionResolution: 2.81→71.84 Å / Num. obs: 10268 / % possible obs: 99.9 % / Redundancy: 6.6 % / Biso Wilson estimate: 48.71 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.118 / Net I/σ(I): 9.6
Reflection shellResolution: 2.81→2.96 Å / Num. unique obs: 1470 / CC1/2: 0.963

-
Processing

Software
NameVersionClassification
PHENIXdev_4694refinement
MOSFLMdata reduction
pointlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1JNK

1jnk


Resolution: 2.81→59.68 Å / SU ML: 0.3931 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 34.1849
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2948 488 4.79 %
Rwork0.2361 9706 -
obs0.239 10194 99.66 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 63.43 Å2
Refinement stepCycle: LAST / Resolution: 2.81→59.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2682 0 37 0 2719
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00472782
X-RAY DIFFRACTIONf_angle_d0.54273769
X-RAY DIFFRACTIONf_chiral_restr0.0385414
X-RAY DIFFRACTIONf_plane_restr0.0035474
X-RAY DIFFRACTIONf_dihedral_angle_d20.04241036
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.81-3.220.39841600.31363158X-RAY DIFFRACTION99.22
3.22-4.050.3161690.23523194X-RAY DIFFRACTION99.79
4.05-59.680.24611590.21163354X-RAY DIFFRACTION99.94
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
15.616539387670.2185102440160.3412948666884.477962768921.066888130797.46019735044-0.0449689976542-0.637009402843-0.1260786901721.104411196290.571797603133-0.2614391514880.03803756047721.08215374108-0.6861709709960.8209260964720.0521077771261-0.1105521948380.483417246055-0.07149900292130.40727104581225.813189325410.312287515445.9678615395
21.07763368612-1.226108987440.8923641901582.61100721099-0.1844602180242.37952777496-0.1534856149030.2510240825120.09578218564910.231238430289-0.148989254322-0.2986129931050.558866440747-0.05009316054870.2860292392150.636008546572-0.1301383450870.06057205776210.445723275903-0.01674320453020.33870929840116.058317310115.29751333737.7172780036
31.776591640410.9874390221021.73086985662.617567972280.1080328442674.344673624090.06667770252220.192137261027-0.0825673481320.158761863195-0.157374808452-0.1499770758650.3217650278780.03436707775780.04976370334880.471164017223-0.01507212307010.04066128518460.308400190673-0.01791177425120.30531221667915.812594814510.850528589127.248212767
41.804085725221.61524178055-0.9352776986186.59346992682.179864527922.292359035990.211893291446-0.09586969222950.117611556616-0.1606001169760.0337219180906-0.0190241824649-1.101542897180.2819556866120.03183917591490.690461458101-0.14378346832-0.01454155692410.376510095888-0.04582228873230.27687520967921.275822931525.812706245719.3178577623
53.061508922241.597708918270.7160529840224.275484087990.7093019175343.17678586687-0.1562790354160.3547935885160.197327057691-0.9012151674250.23637546989-0.234169441586-0.6581005248090.436954460633-0.1053316491040.684735035335-0.02406395931580.05447317782110.423231428849-0.06021479000620.4167533414820.512729869822.13701452485.36070111978
62.669894237543.805336706640.9295325971745.46159027561.245036252652.920920758460.143861399986-0.101276044955-0.501505203968-0.7872850631040.174265083808-0.5633257345960.2754056678730.284619372951-0.2969460244350.6238810921230.1306825888580.02854444323690.377232097278-0.02970174678250.43057694020415.41768819751.594754791972.67925820019
71.4485940287-0.3295814270411.917755032730.8102081212510.9395272317335.098546789980.0371797961057-0.2737130783230.1968789854130.108002639499-0.3732197974230.45715589261-0.732630052975-0.9427244793160.3070512025450.728095727772-0.08940067203280.09586837163590.451088579889-0.03088919729320.3779427364419.321506550418.721238054723.9413218101
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11chain 'A' and (resid 45 through 75 )45 - 751 - 31
22chain 'A' and (resid 76 through 130 )76 - 13032 - 86
33chain 'A' and (resid 131 through 210 )131 - 21087 - 166
44chain 'A' and (resid 211 through 241 )211 - 241167 - 192
55chain 'A' and (resid 242 through 312 )242 - 312193 - 263
66chain 'A' and (resid 313 through 339 )313 - 339264 - 290
77chain 'A' and (resid 340 through 400 )340 - 400291 - 333

+
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://pdbjlvh1.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