[English] 日本語
Yorodumi
- PDB-7chm: Crystal structure of TTK kinase domain in complex with compound 8 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7chm
TitleCrystal structure of TTK kinase domain in complex with compound 8
ComponentsDual specificity protein kinase TTK
KeywordsTRANSFERASE / Kinase MPS1 TTK Structure-guided drug design
Function / homology
Function and homology information


protein localization to meiotic spindle midzone / meiotic spindle assembly checkpoint signaling / repair of mitotic kinetochore microtubule attachment defect / kinetochore binding / female meiosis chromosome segregation / protein localization to kinetochore / dual-specificity kinase / spindle organization / mitotic spindle assembly checkpoint signaling / positive regulation of SMAD protein signal transduction ...protein localization to meiotic spindle midzone / meiotic spindle assembly checkpoint signaling / repair of mitotic kinetochore microtubule attachment defect / kinetochore binding / female meiosis chromosome segregation / protein localization to kinetochore / dual-specificity kinase / spindle organization / mitotic spindle assembly checkpoint signaling / positive regulation of SMAD protein signal transduction / protein serine/threonine/tyrosine kinase activity / mitotic spindle organization / chromosome segregation / kinetochore / spindle / protein tyrosine kinase activity / histone H3Y41 kinase activity / histone H2AXY142 kinase activity / protein serine kinase activity / protein serine/threonine kinase activity / positive regulation of cell population proliferation / ATP binding / identical protein binding / nucleus / membrane / cytoplasm
Similarity search - Function
Protein kinase Mps1 family / Tetratricopeptide-like helical domain superfamily / 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-FZF / Dual specificity protein kinase TTK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.65 Å
AuthorsKim, H.L. / Cho, H.Y. / Park, Y.W. / Lee, Y.H. / Son, J.B. / Ko, E.H. / Choi, H.G. / Kim, N.D.
CitationJournal: J.Med.Chem. / Year: 2021
Title: X-ray Crystal Structure-Guided Design and Optimization of 7 H -Pyrrolo[2,3- d ]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor.
Authors: Lee, Y. / Kim, H. / Kim, H. / Cho, H.Y. / Jee, J.G. / Seo, K.A. / Son, J.B. / Ko, E. / Choi, H.G. / Kim, N.D. / Kim, I.
History
DepositionJul 6, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0May 12, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 9, 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 1.2Nov 29, 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
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dual specificity protein kinase TTK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,0952
Polymers32,6191
Non-polymers4761
Water1086
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area12860 Å2
Unit cell
Length a, b, c (Å)70.492, 108.975, 113.134
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number23
Space group name H-MI222
Space group name HallI22
Symmetry operation#1: x,y,z
#2: x,-y,-z
#3: -x,y,-z
#4: -x,-y,z
#5: x+1/2,y+1/2,z+1/2
#6: x+1/2,-y+1/2,-z+1/2
#7: -x+1/2,y+1/2,-z+1/2
#8: -x+1/2,-y+1/2,z+1/2

-
Components

#1: Protein Dual specificity protein kinase TTK / Phosphotyrosine picked threonine-protein kinase / PYT


Mass: 32619.260 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TTK, MPS1, MPS1L1 / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P33981, dual-specificity kinase
#2: Chemical ChemComp-FZF / 4-(cyclohexylamino)-2-[(2-methoxy-4-morpholin-4-ylcarbonyl-phenyl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile


Mass: 475.543 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H29N7O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.33 Å3/Da / Density % sol: 63.07 %
Crystal growTemperature: 294.15 K / Method: vapor diffusion, sitting drop / pH: 6
Details: 7-9% PEG 10000, 0.08-0.14 M magnesium acetate, 0.1 M MES pH 6.0

-
Data collection

DiffractionMean temperature: 294.15 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PAL/PLS / Beamline: 5C (4A) / Wavelength: 0.9795 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 31, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.65→50 Å / Num. obs: 13070 / % possible obs: 100 % / Redundancy: 6.6 % / Biso Wilson estimate: 75.95 Å2 / CC1/2: 0.992 / Net I/σ(I): 35.351
Reflection shellResolution: 2.65→2.7 Å / Rmerge(I) obs: 0.71 / Num. unique obs: 655 / CC1/2: 0.852 / Rpim(I) all: 0.301 / Rsym value: 0.71

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6B4W

6b4w


Resolution: 2.65→40.89 Å / SU ML: 0.3814 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 28.7501
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2531 1296 9.96 %
Rwork0.2077 11713 -
obs0.2122 13009 99.8 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 82.7 Å2
Refinement stepCycle: LAST / Resolution: 2.65→40.89 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2105 0 35 6 2146
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01012190
X-RAY DIFFRACTIONf_angle_d1.16192971
X-RAY DIFFRACTIONf_chiral_restr0.0607323
X-RAY DIFFRACTIONf_plane_restr0.0065372
X-RAY DIFFRACTIONf_dihedral_angle_d21.3766300
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.65-2.760.33671440.28891280X-RAY DIFFRACTION98.96
2.76-2.880.33751400.26931278X-RAY DIFFRACTION100
2.88-3.030.31321420.25681269X-RAY DIFFRACTION99.79
3.03-3.220.32161440.25311293X-RAY DIFFRACTION100
3.22-3.470.28681410.24821288X-RAY DIFFRACTION100
3.47-3.820.27781440.22051288X-RAY DIFFRACTION100
3.82-4.370.25091420.1981307X-RAY DIFFRACTION99.79
4.37-5.50.2491490.18131314X-RAY DIFFRACTION99.93
5.51-40.890.19781500.18631396X-RAY DIFFRACTION99.81

+
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