[English] 日本語
Yorodumi
- PDB-5lxc: Crystal structure of DYRK2 in complex with EHT 5372 (Compound 1) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5lxc
TitleCrystal structure of DYRK2 in complex with EHT 5372 (Compound 1)
ComponentsDual specificity tyrosine-phosphorylation-regulated kinase 2
KeywordsTRANSFERASE / kinase / inhibitor / unusual binding mode / Structural Genomics / Structural Genomics Consortium / SGC
Function / homology
Function and homology information


dual-specificity kinase / negative regulation of calcineurin-NFAT signaling cascade / smoothened signaling pathway / positive regulation of glycogen biosynthetic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / ubiquitin ligase complex / protein serine/threonine/tyrosine kinase activity / regulation of signal transduction by p53 class mediator / manganese ion binding / protein tyrosine kinase activity ...dual-specificity kinase / negative regulation of calcineurin-NFAT signaling cascade / smoothened signaling pathway / positive regulation of glycogen biosynthetic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / ubiquitin ligase complex / protein serine/threonine/tyrosine kinase activity / regulation of signal transduction by p53 class mediator / manganese ion binding / protein tyrosine kinase activity / Regulation of TP53 Activity through Phosphorylation / cytoskeleton / ribonucleoprotein complex / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / DNA damage response / magnesium ion binding / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Dual specificity tyrosine-phosphorylation-regulated kinase / : / 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, ATP binding site / Protein kinases ATP-binding region signature. ...Dual specificity tyrosine-phosphorylation-regulated kinase / : / 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, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-7AA / Dual specificity tyrosine-phosphorylation-regulated kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsChaikuad, A. / von Delft, F. / Arrowsmith, C.H. / Edwards, A. / Bountra, C. / Besson, T. / Knapp, S. / Structural Genomics Consortium (SGC)
CitationJournal: J. Med. Chem. / Year: 2016
Title: An Unusual Binding Model of the Methyl 9-Anilinothiazolo[5,4-f] quinazoline-2-carbimidates (EHT 1610 and EHT 5372) Confers High Selectivity for Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases.
Authors: Chaikuad, A. / Diharce, J. / Schroder, M. / Foucourt, A. / Leblond, B. / Casagrande, A.S. / Desire, L. / Bonnet, P. / Knapp, S. / Besson, T.
History
DepositionSep 20, 2016Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 26, 2016Provider: repository / Type: Initial release
Revision 1.1Jan 11, 2017Group: Database references
Revision 1.2Nov 20, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dual specificity tyrosine-phosphorylation-regulated kinase 2
B: Dual specificity tyrosine-phosphorylation-regulated kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)95,43015
Polymers93,9392
Non-polymers1,49113
Water7,134396
1
A: Dual specificity tyrosine-phosphorylation-regulated kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,87010
Polymers46,9691
Non-polymers9019
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Dual specificity tyrosine-phosphorylation-regulated kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,5605
Polymers46,9691
Non-polymers5904
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)130.220, 60.980, 148.790
Angle α, β, γ (deg.)90.00, 105.04, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11B-687-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12A
22B
13B
23A
14B
24A

NCS domain segments:
Dom-IDComponent-IDEns-IDRefine codeAuth asym-IDAuth seq-ID
1112A81 - 110
2112B81 - 110
1214A111 - 144
2214B111 - 144
1122A145 - 390
2122B145 - 390
1134B391 - 420
2134A391 - 420
1142B421 - 464
2142A421 - 464

NCS ensembles :
ID
1
2
3
4

NCS oper:
IDCodeMatrixVector
1given(1), (1), (1)
2given(-0.020111, 0.509966, -0.859959), (0.677581, -0.625523, -0.386788), (-0.735173, -0.59047, -0.332964)81.692833, -9.08403, 90.697693
3given(1), (1), (1)
4given(0.009743, 0.568123, -0.822886), (0.637234, -0.637711, -0.432732), (-0.770608, -0.520155, -0.368241)77.363777, -3.67951, 94.869568
5given(1), (1), (1)
6given(-0.028827, 0.631161, -0.775116), (0.574354, -0.624191, -0.529626), (-0.8181, -0.460458, -0.344516)77.39283, 2.9148, 96.982986
7given(1), (1), (1)
8given(0.005589, 0.633686, -0.77357), (0.573182, -0.63592, -0.516786), (-0.819409, -0.440508, -0.366772)75.005257, 2.64265, 97.018356

-
Components

#1: Protein Dual specificity tyrosine-phosphorylation-regulated kinase 2


Mass: 46969.293 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DYRK2 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): R3-pRARE2 / References: UniProt: Q92630, dual-specificity kinase
#2: Chemical ChemComp-7AA / methyl 9-[(2,4-dichlorophenyl)amino]-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate


Mass: 404.273 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C17H11Cl2N5OS
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 11 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 396 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.04 Å3/Da / Density % sol: 59.5 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 25% PEG 3350, 0.2 M NaCl and 0.1 M bis-tris, pH 5.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.92 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Dec 19, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.92 Å / Relative weight: 1
ReflectionResolution: 2.15→49.43 Å / Num. obs: 60094 / % possible obs: 97.6 % / Redundancy: 4 % / Biso Wilson estimate: 26.4 Å2 / Rmerge(I) obs: 0.107 / Net I/σ(I): 8.2
Reflection shellResolution: 2.15→2.27 Å / Redundancy: 4 % / Rmerge(I) obs: 0.578 / Mean I/σ(I) obs: 2.1 / % possible all: 98.7

-
Processing

Software
NameVersionClassification
REFMAC5.7.0032refinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.15→49.43 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.914 / SU B: 13.049 / SU ML: 0.172 / Cross valid method: THROUGHOUT / ESU R: 0.215 / ESU R Free: 0.193 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25401 3047 5.1 %RANDOM
Rwork0.20564 ---
obs0.20808 57045 97.33 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 49.867 Å2
Baniso -1Baniso -2Baniso -3
1--1.8 Å20 Å21.67 Å2
2---2.92 Å2-0 Å2
3---3.73 Å2
Refine analyzeLuzzati coordinate error obs: 0.318 Å
Refinement stepCycle: 1 / Resolution: 2.15→49.43 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6215 0 96 396 6707
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0196520
X-RAY DIFFRACTIONr_bond_other_d0.0040.026263
X-RAY DIFFRACTIONr_angle_refined_deg1.4431.9788784
X-RAY DIFFRACTIONr_angle_other_deg0.8233.00114400
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2435788
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.02823.269309
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.797151167
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.9181552
X-RAY DIFFRACTIONr_chiral_restr0.0820.2908
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0217322
X-RAY DIFFRACTIONr_gen_planes_other0.0040.021576
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_it1.642.4013098
X-RAY DIFFRACTIONr_mcbond_other1.6392.4013097
X-RAY DIFFRACTIONr_mcangle_it2.5263.5963874
X-RAY DIFFRACTIONr_mcangle_other2.5253.5963875
X-RAY DIFFRACTIONr_scbond_it2.142.6743422
X-RAY DIFFRACTIONr_scbond_other2.1362.6743422
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other3.3153.8974901
X-RAY DIFFRACTIONr_long_range_B_refined5.95920.2657751
X-RAY DIFFRACTIONr_long_range_B_other5.95920.2717752
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Dom-ID: 1 / Refine-ID: X-RAY DIFFRACTION

Ens-IDAuth asym-IDNumberTypeRms dev position (Å)Weight position
1A788MEDIUM POSITIONAL0.350.5
1A178TIGHT THERMAL1.580.5
1A788MEDIUM THERMAL2.512
2A2537MEDIUM POSITIONAL0.050.5
2A1447TIGHT THERMAL2.060.5
2A2537MEDIUM THERMAL3.242
3B421MEDIUM POSITIONAL0.340.5
3B421MEDIUM THERMAL3.822
4B420MEDIUM POSITIONAL0.140.5
4B249TIGHT THERMAL1.930.5
4B420MEDIUM THERMAL2.342
LS refinement shellResolution: 2.15→2.206 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.336 220 -
Rwork0.305 4278 -
obs--98.86 %
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)
15.3451.8306-0.12748.8679-1.12672.7516-0.18530.1281-0.373-0.35950.1768-0.4880.2359-0.04260.00850.1063-0.02080.0280.02230.01420.098233.3243-8.363816.3025
24.56921.8511-0.35783.7181-0.00531.2309-0.0765-0.12090.1158-0.13980.05110.01960.1726-0.06450.02540.06570.0066-0.02090.0285-0.00250.067341.367517.609617.8013
33.8844-0.20291.13682.1533-0.1591.6564-0.161-0.35520.68720.1939-0.056-0.1371-0.23370.13390.2170.0699-0.0118-0.03130.0831-0.06360.312960.385232.644828.1881
44.1006-0.2859-0.2991.43050.14864.85080.3053-0.47920.5540.0613-0.06310.039-0.5944-0.1742-0.24220.6212-0.00030.35650.6478-0.01980.53356.848318.532964.8652
56.481-1.124-4.54335.73461.89443.5790.2785-0.20660.10580.2671-0.11220.2928-0.0793-0.1595-0.16630.4335-0.04570.11960.58560.16660.227966.95035.615555.725
62.4338-0.12750.25341.909-0.3422.6686-0.0204-0.2793-0.17770.01570.01340.0090.1585-0.0310.0070.02970.0110.02790.03820.02710.055375.95613.199129.7048
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A80 - 154
2X-RAY DIFFRACTION2A155 - 307
3X-RAY DIFFRACTION3A308 - 464
4X-RAY DIFFRACTION4B80 - 161
5X-RAY DIFFRACTION5B162 - 230
6X-RAY DIFFRACTION6B231 - 465

+
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