[English] 日本語
Yorodumi
- PDB-5ap6: Naturally Occurring Mutations in the MPS1 Gene Predispose Cells t... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ap6
TitleNaturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance.
ComponentsDUAL SPECIFICITY PROTEIN KINASE TTK
KeywordsTRANSFERASE / MPS1 / MITOSIS
Function / homology
Function and homology information


protein localization to meiotic spindle midzone / meiotic spindle assembly checkpoint signaling / kinetochore binding / female meiosis chromosome segregation / protein localization to kinetochore / dual-specificity kinase / spindle organization / mitotic spindle assembly checkpoint signaling / protein serine/threonine/tyrosine kinase activity / mitotic spindle organization ...protein localization to meiotic spindle midzone / meiotic spindle assembly checkpoint signaling / kinetochore binding / female meiosis chromosome segregation / protein localization to kinetochore / dual-specificity kinase / spindle organization / mitotic spindle assembly checkpoint signaling / protein serine/threonine/tyrosine kinase activity / mitotic spindle organization / chromosome segregation / spindle / kinetochore / protein tyrosine kinase activity / phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / positive regulation of cell population proliferation / ATP binding / membrane / identical protein binding / nucleus / cytoplasm
Similarity search - Function
Protein kinase Mps1 family / Tetratricopeptide-like helical domain superfamily / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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 Mps1 family / Tetratricopeptide-like helical domain superfamily / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-PWU / Dual specificity protein kinase TTK
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsGurden, M.D. / Westwood, I.M. / Faisal, A. / Naud, S. / Cheung, K.M. / McAndrew, C. / Wood, A. / Schmitt, J. / Boxall, K. / Mak, G. ...Gurden, M.D. / Westwood, I.M. / Faisal, A. / Naud, S. / Cheung, K.M. / McAndrew, C. / Wood, A. / Schmitt, J. / Boxall, K. / Mak, G. / Workman, P. / Burke, R. / Hoelder, S. / Blagg, J. / van Montfort, R. / Linardopoulos, S.
CitationJournal: Cancer Res. / Year: 2015
Title: Naturally Occurring Mutations in the Mps1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance.
Authors: Gurden, M.D. / Westwood, I.M. / Faisal, A. / Naud, S. / Cheung, K.J. / Mcandrew, C. / Wood, A. / Schmitt, J. / Boxall, K. / Mak, G. / Workman, P. / Burke, R. / Hoelder, S. / Blagg, J. / Van ...Authors: Gurden, M.D. / Westwood, I.M. / Faisal, A. / Naud, S. / Cheung, K.J. / Mcandrew, C. / Wood, A. / Schmitt, J. / Boxall, K. / Mak, G. / Workman, P. / Burke, R. / Hoelder, S. / Blagg, J. / Van Montfort, R.L.M. / Linardopoulos, S.
History
DepositionSep 14, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 23, 2015Provider: repository / Type: Initial release
Revision 1.1Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)37,36713
Polymers36,1981
Non-polymers1,16812
Water1,13563
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)69.720, 104.370, 112.190
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein DUAL SPECIFICITY PROTEIN KINASE TTK / PHOSPHOTYROSINE PICKED THREONINE-PROTEIN KINASE / PYT / MONOPOLAR SPINDLE KINASE 1


Mass: 36198.320 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, RESIDUES 519-808 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / Variant (production host): AI / References: UniProt: P33981, dual-specificity kinase
#2: Chemical ChemComp-PWU / ISOPROPYL 6-((4-(1,2-DIMETHYL-1H-IMIDAZOL-5-YL)PHENYL)AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)-1H-PYRROLO[3,2-C]PYRIDINE-1-CARBOXYLATE


Mass: 469.538 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H27N7O2
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE / Dimethyl sulfoxide


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 63 / Source method: isolated from a natural source / Formula: H2O
Compound detailsENGINEERED RESIDUE IN CHAIN A, CYS 604 TO TRP
Sequence detailsTHE SEQUENCE INCLUDING HEXAHISTIDINE TAG IS AS DESCRIBED IN NAT. CHEM. BIOL. 2010, 6, 259-368 WITH ...THE SEQUENCE INCLUDING HEXAHISTIDINE TAG IS AS DESCRIBED IN NAT. CHEM. BIOL. 2010, 6, 259-368 WITH AN ADDITIONAL MUTATION C604W

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.82 Å3/Da / Density % sol: 56.37 % / Description: NONE
Crystal growpH: 7.5 / Details: 38% (V/V) PEG300, PH 7.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.9686
DetectorType: DECTRIS PILATUS / Detector: PIXEL / Date: Dec 8, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9686 Å / Relative weight: 1
ReflectionResolution: 2.1→40.31 Å / Num. obs: 24232 / % possible obs: 99.9 % / Observed criterion σ(I): 0 / Redundancy: 4.3 % / Biso Wilson estimate: 52.54 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 9.5
Reflection shellResolution: 2.1→2.16 Å / Redundancy: 3.8 % / Mean I/σ(I) obs: 0.6 / % possible all: 99.3

-
Processing

Software
NameVersionClassification
BUSTER2.11.4refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 4C4J

4c4j


Resolution: 2.1→40.31 Å / Cor.coef. Fo:Fc: 0.9616 / Cor.coef. Fo:Fc free: 0.9551 / SU R Cruickshank DPI: 0.146 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.145 / SU Rfree Blow DPI: 0.132 / SU Rfree Cruickshank DPI: 0.133
RfactorNum. reflection% reflectionSelection details
Rfree0.2089 1233 5.11 %RANDOM
Rwork0.1822 ---
obs0.1835 24151 99.49 %-
Displacement parametersBiso mean: 64.45 Å2
Baniso -1Baniso -2Baniso -3
1-5.2651 Å20 Å20 Å2
2---6.2637 Å20 Å2
3---0.9985 Å2
Refine analyzeLuzzati coordinate error obs: 0.292 Å
Refinement stepCycle: LAST / Resolution: 2.1→40.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2077 0 79 63 2219
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.012205HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.082977HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d748SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes55HARMONIC2
X-RAY DIFFRACTIONt_gen_planes341HARMONIC5
X-RAY DIFFRACTIONt_it2205HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.12
X-RAY DIFFRACTIONt_other_torsion19.08
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion287SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2465SEMIHARMONIC4
LS refinement shellResolution: 2.1→2.19 Å / Total num. of bins used: 12
RfactorNum. reflection% reflection
Rfree0.2493 158 5.63 %
Rwork0.2603 2646 -
all0.2597 2804 -
obs--99.49 %
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)
13.30561.3151-1.08431.51360.52182.76810.0705-0.073-0.04660.1377-0.0420.01590.0690.03-0.0285-0.1226-0.0132-0.02990.0713-0.0573-0.1917-36.4039-20.3739-16.2342
21.8883-1.29960.26832.62340.93162.24760.08370.12840.3059-0.3224-0.0136-0.3476-0.37420.0059-0.0701-0.12460.00170.04540.1194-0.0225-0.1542-23.1396-8.0669-29.6437
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{A|516 - 662}
2X-RAY DIFFRACTION2{A|663 - 794}

+
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