[English] 日本語
Yorodumi
- PDB-7avq: Crystal structure of haspin in complex with disubstituted imidazo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7avq
TitleCrystal structure of haspin in complex with disubstituted imidazo[1,2- b]pyridazine inhibitor (compound 12)
ComponentsSerine/threonine-protein kinase haspin
KeywordsTRANSFERASE / kinase / haspin / GSG2 / inhibitor / Structural Genomics / Structural Genomics Consortium / SGC
Function / homology
Function and homology information


histone H3T3 kinase activity / protein localization to chromosome, centromeric region / mitotic sister chromatid cohesion / mitotic spindle assembly checkpoint signaling / spindle / mitotic cell cycle / chromosome / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction ...histone H3T3 kinase activity / protein localization to chromosome, centromeric region / mitotic sister chromatid cohesion / mitotic spindle assembly checkpoint signaling / spindle / mitotic cell cycle / chromosome / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / protein phosphorylation / protein serine kinase activity / centrosome / nucleoplasm / ATP binding / nucleus / cytoplasm
Similarity search - Function
Serine/threonine-protein kinase haspin, C-terminal / Haspin like kinase domain / Domain of unknown function / 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-S1Z / Serine/threonine-protein kinase haspin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.65 Å
AuthorsChaikuad, A. / Bonnet, P. / Routier, S. / Knapp, S. / Structural Genomics Consortium (SGC)
CitationJournal: J Enzyme Inhib Med Chem / Year: 2020
Title: Design of new disubstituted imidazo[1,2- b ]pyridazine derivatives as selective Haspin inhibitors. Synthesis, binding mode and anticancer biological evaluation.
Authors: Elie, J. / Feizbakhsh, O. / Desban, N. / Josselin, B. / Baratte, B. / Bescond, A. / Duez, J. / Fant, X. / Bach, S. / Marie, D. / Place, M. / Ben Salah, S. / Chartier, A. / Berteina-Raboin, S. ...Authors: Elie, J. / Feizbakhsh, O. / Desban, N. / Josselin, B. / Baratte, B. / Bescond, A. / Duez, J. / Fant, X. / Bach, S. / Marie, D. / Place, M. / Ben Salah, S. / Chartier, A. / Berteina-Raboin, S. / Chaikuad, A. / Knapp, S. / Carles, F. / Bonnet, P. / Buron, F. / Routier, S. / Ruchaud, S.
History
DepositionNov 5, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 18, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 8, 2021Group: Database references / Structure summary / Category: audit_author / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)41,3596
Polymers40,7111
Non-polymers6485
Water5,296294
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area950 Å2
ΔGint-23 kcal/mol
Surface area15140 Å2
Unit cell
Length a, b, c (Å)70.349, 78.009, 86.150
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Serine/threonine-protein kinase haspin / Germ cell-specific gene 2 protein / H-haspin / Haploid germ cell-specific nuclear protein kinase


Mass: 40711.484 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HASPIN, GSG2 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): -R3-pRARE2
References: UniProt: Q8TF76, non-specific serine/threonine protein kinase

-
Non-polymers , 5 types, 299 molecules

#2: Chemical ChemComp-S1Z / (2~{R})-2-[[3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-6-yl]amino]butan-1-ol


Mass: 322.364 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H18N6O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-MPD / (4S)-2-METHYL-2,4-PENTANEDIOL


Mass: 118.174 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H14O2 / Comment: precipitant*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 294 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.9 Å3/Da / Density % sol: 57.63 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, sitting drop / Details: 63% MPD and 0.1 M SPG, pH 6.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97626 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 18, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97626 Å / Relative weight: 1
ReflectionResolution: 1.65→57.83 Å / Num. obs: 56638 / % possible obs: 98.3 % / Redundancy: 5.3 % / CC1/2: 0.998 / Rmerge(I) obs: 0.067 / Rpim(I) all: 0.031 / Rrim(I) all: 0.074 / Net I/av σ(I): 4.8 / Net I/σ(I): 11.9
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) all% possible allRsym value
1.65-1.745.10.7762.280800.7160.370.86297.1
1.74-1.845.30.4571.676690.2150.50697.80.457
1.84-1.975.30.2562.872430.120.284980.256
1.97-2.135.40.1464.767930.0680.16298.50.146
2.13-2.335.30.1016.763030.0480.11298.50.101
2.33-2.615.30.0768.356980.0360.08598.50.076
2.61-3.015.40.0629.451090.0290.06999.50.062
3.01-3.695.40.04911.443290.0230.055990.049
3.69-5.225.20.04712.734250.0220.05299.40.047
5.22-54.4950.056.419890.0240.05599.50.05

-
Processing

Software
NameVersionClassification
SCALA3.3.22data scaling
REFMAC5.8.0131refinement
PDB_EXTRACT3.27data extraction
iMOSFLMdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4OUC

4ouc


Resolution: 1.65→57.83 Å / Cor.coef. Fo:Fc: 0.975 / Cor.coef. Fo:Fc free: 0.969 / SU B: 3.336 / SU ML: 0.056 / SU R Cruickshank DPI: 0.0725 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.073 / ESU R Free: 0.072 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.1794 2837 5 %RANDOM
Rwork0.1593 ---
obs0.1603 53758 98.05 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 81.47 Å2 / Biso mean: 32.098 Å2 / Biso min: 17.1 Å2
Baniso -1Baniso -2Baniso -3
1-1.49 Å20 Å20 Å2
2--0.21 Å2-0 Å2
3----1.69 Å2
Refinement stepCycle: final / Resolution: 1.65→57.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2627 0 45 294 2966
Biso mean--32.47 41.22 -
Num. residues----328
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0192803
X-RAY DIFFRACTIONr_bond_other_d0.0020.022698
X-RAY DIFFRACTIONr_angle_refined_deg1.611.9623804
X-RAY DIFFRACTIONr_angle_other_deg0.91736240
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2925351
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.78124.444126
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.8315511
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.8221513
X-RAY DIFFRACTIONr_chiral_restr0.1010.2425
X-RAY DIFFRACTIONr_gen_planes_refined0.010.023256
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02647
LS refinement shellResolution: 1.65→1.693 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.282 215 -
Rwork0.266 3847 -
all-4062 -
obs--96.03 %
Refinement TLS params.Method: refined / Origin x: 80.5891 Å / Origin y: 72.0721 Å / Origin z: 35.1926 Å
111213212223313233
T0.0145 Å2-0.0028 Å2-0.002 Å2-0.0371 Å20.0204 Å2--0.014 Å2
L1.0084 °20.4668 °20.1761 °2-2.1837 °20.9572 °2--1.7709 °2
S-0.0108 Å °-0.1154 Å °-0.0432 Å °0.1253 Å °-0.0229 Å °-0.0343 Å °0.1301 Å °-0.0031 Å °0.0336 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