[English] 日本語
Yorodumi
- PDB-7a51: Structure of DYRK1A in complex with compound 5 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7a51
TitleStructure of DYRK1A in complex with compound 5
ComponentsDual specificity tyrosine-phosphorylation-regulated kinase 1ADYRK1A
KeywordsTRANSFERASE / SERINE/THREONINE-PROTEIN KINASE / PHOSPHOPROTEIN / KINASE / SBDD / FBLD / SMALL MOLECULE INHIBITOR
Function / homology
Function and homology information


histone H3T45 kinase activity / positive regulation of protein deacetylation / peptidyl-serine autophosphorylation / negative regulation of DNA methylation-dependent heterochromatin formation / dual-specificity kinase / [RNA-polymerase]-subunit kinase / negative regulation of microtubule polymerization / tau-protein kinase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of mRNA splicing, via spliceosome ...histone H3T45 kinase activity / positive regulation of protein deacetylation / peptidyl-serine autophosphorylation / negative regulation of DNA methylation-dependent heterochromatin formation / dual-specificity kinase / [RNA-polymerase]-subunit kinase / negative regulation of microtubule polymerization / tau-protein kinase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of mRNA splicing, via spliceosome / amyloid-beta formation / G0 and Early G1 / peptidyl-tyrosine autophosphorylation / cytoskeletal protein binding / protein serine/threonine/tyrosine kinase activity / tubulin binding / RNA polymerase II CTD heptapeptide repeat kinase activity / positive regulation of RNA splicing / peptidyl-threonine phosphorylation / non-membrane spanning protein tyrosine kinase activity / tau protein binding / circadian rhythm / peptidyl-tyrosine phosphorylation / : / nervous system development / actin binding / peptidyl-serine phosphorylation / protein tyrosine kinase activity / protein autophosphorylation / transcription coactivator activity / cytoskeleton / protein kinase activity / nuclear speck / ribonucleoprotein complex / axon / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / dendrite / positive regulation of DNA-templated transcription / nucleoplasm / ATP binding / identical protein binding / nucleus / cytoplasm
Similarity search - Function
Dual specificity tyrosine-phosphorylation-regulated kinase 1A/1B, catalytic domain / 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
Similarity search - Domain/homology
Chem-QYK / Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.9 Å
AuthorsDokurno, P. / Surgenor, A.E. / Hubbard, R.E.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Fragment-Derived Selective Inhibitors of Dual-Specificity Kinases DYRK1A and DYRK1B.
Authors: Lee Walmsley, D. / Murray, J.B. / Dokurno, P. / Massey, A.J. / Benwell, K. / Fiumana, A. / Foloppe, N. / Ray, S. / Smith, J. / Surgenor, A.E. / Edmonds, T. / Demarles, D. / Burbridge, M. / ...Authors: Lee Walmsley, D. / Murray, J.B. / Dokurno, P. / Massey, A.J. / Benwell, K. / Fiumana, A. / Foloppe, N. / Ray, S. / Smith, J. / Surgenor, A.E. / Edmonds, T. / Demarles, D. / Burbridge, M. / Cruzalegui, F. / Kotschy, A. / Hubbard, R.E.
History
DepositionAug 20, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 30, 2021Provider: repository / Type: Initial release
Revision 1.1Jul 21, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 31, 2024Group: 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: Dual specificity tyrosine-phosphorylation-regulated kinase 1A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,8992
Polymers41,6471
Non-polymers2521
Water4,378243
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area15510 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.512, 81.512, 123.668
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212
Components on special symmetry positions
IDModelComponents
11A-737-

HOH

-
Components

#1: Protein Dual specificity tyrosine-phosphorylation-regulated kinase 1A / DYRK1A / Dual specificity YAK1-related kinase / HP86 / Protein kinase minibrain homolog / hMNB


Mass: 41647.129 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DYRK1A, DYRK, MNB, MNBH / Cell line (production host): pLysS / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q13627, dual-specificity kinase
#2: Chemical ChemComp-QYK / 4-azanyl-6-bromanyl-7-methyl-pyrrolo[2,3-d]pyrimidine-5-carbonitrile


Mass: 252.071 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H6BrN5 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 243 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.47 Å3/Da / Density % sol: 50.13 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: 0.1M MES buffer at pH 6.5, 12% Peg3350, 0.2M MgCl2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 26, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 1.9→50 Å / Num. obs: 32664 / % possible obs: 97.2 % / Redundancy: 6.5 % / Rmerge(I) obs: 0.096 / Net I/σ(I): 18.2
Reflection shellResolution: 1.9→1.97 Å / Rmerge(I) obs: 0.812 / Mean I/σ(I) obs: 1.7 / Num. unique obs: 3236

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
REFMAC5.8.0258refinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2vx3

2vx3


Resolution: 1.9→25 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.947 / SU B: 3.574 / SU ML: 0.1 / SU R Cruickshank DPI: 0.1333 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.133 / ESU R Free: 0.132 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2196 1635 5 %RANDOM
Rwork0.1743 ---
obs0.1765 30994 97.23 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 114.9 Å2 / Biso mean: 32.469 Å2 / Biso min: 14.07 Å2
Baniso -1Baniso -2Baniso -3
1-1.35 Å2-0 Å2-0 Å2
2--1.35 Å2-0 Å2
3----2.7 Å2
Refinement stepCycle: final / Resolution: 1.9→25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2692 0 14 243 2949
Biso mean--34.6 40.88 -
Num. residues----331
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0132769
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172617
X-RAY DIFFRACTIONr_angle_refined_deg1.571.6433735
X-RAY DIFFRACTIONr_angle_other_deg1.3791.5786070
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.845329
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.72521.944144
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.03915509
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.5241518
X-RAY DIFFRACTIONr_chiral_restr0.080.2344
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.023027
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02589
LS refinement shellResolution: 1.9→2.002 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.264 218 -
Rwork0.258 4483 -
all-4701 -
obs--98.8 %

+
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