[English] 日本語
Yorodumi
- PDB-4d2p: Structure of MELK in complex with inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4d2p
TitleStructure of MELK in complex with inhibitors
ComponentsMATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
KeywordsTRANSFERASE / FRAGMENT STERBASED DRUG DESIGN / KINASE
Function / homology
Function and homology information


neural precursor cell proliferation / intrinsic apoptotic signaling pathway in response to oxidative stress / hemopoiesis / non-membrane spanning protein tyrosine kinase activity / non-specific protein-tyrosine kinase / G2/M transition of mitotic cell cycle / protein autophosphorylation / cell cortex / cell population proliferation / non-specific serine/threonine protein kinase ...neural precursor cell proliferation / intrinsic apoptotic signaling pathway in response to oxidative stress / hemopoiesis / non-membrane spanning protein tyrosine kinase activity / non-specific protein-tyrosine kinase / G2/M transition of mitotic cell cycle / protein autophosphorylation / cell cortex / cell population proliferation / non-specific serine/threonine protein kinase / positive regulation of apoptotic process / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / calcium ion binding / lipid binding / ATP binding / membrane / plasma membrane
Similarity search - Function
Maternal embryonic leucine zipper kinase, catalytic domain / : / Maternal embryonic leucine zipper kinase, UBA domain / Kinase associated domain 1 (KA1) / Kinase associated domain 1 / Kinase associated domain 1 (KA1) profile. / KA1 domain/Ssp2, C-terminal / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site ...Maternal embryonic leucine zipper kinase, catalytic domain / : / Maternal embryonic leucine zipper kinase, UBA domain / Kinase associated domain 1 (KA1) / Kinase associated domain 1 / Kinase associated domain 1 (KA1) profile. / KA1 domain/Ssp2, C-terminal / 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-6Z7 / Maternal embryonic leucine zipper kinase
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / OTHER / Resolution: 2.55 Å
AuthorsJohnson, C.N. / Berdini, V. / Beke, L. / Bonnet, P. / Brehmer, D. / Coyle, J.E. / Day, P.J. / Frederickson, M. / Freyne, E.J.E. / Gilissen, R.A.H.J. ...Johnson, C.N. / Berdini, V. / Beke, L. / Bonnet, P. / Brehmer, D. / Coyle, J.E. / Day, P.J. / Frederickson, M. / Freyne, E.J.E. / Gilissen, R.A.H.J. / Hamlett, C.C.F. / Howard, S. / Meerpoel, L. / McMenamin, R. / Patel, S. / Rees, D.C. / Sharff, A. / Sommen, F. / Wu, T. / Linders, J.T.M.
CitationJournal: Acs Med.Chem.Lett. / Year: 2015
Title: Fragment-Based Discovery of Type I Inhibitors of Maternal Embryonic Leucine Zipper Kinase
Authors: Johnson, C.N. / Berdini, V. / Beke, L. / Bonnet, P. / Brehmer, D. / Coyle, J.E. / Day, P.J. / Frederickson, M. / Freyne, E.J.E. / Gilissen, R.A.H.J. / Hamlett, C.C.F. / Howard, S. / ...Authors: Johnson, C.N. / Berdini, V. / Beke, L. / Bonnet, P. / Brehmer, D. / Coyle, J.E. / Day, P.J. / Frederickson, M. / Freyne, E.J.E. / Gilissen, R.A.H.J. / Hamlett, C.C.F. / Howard, S. / Meerpoel, L. / Mcmenamin, R. / Patel, S. / Rees, D.C. / Sharff, A. / Sommen, F. / Wu, T. / Linders, J.T.M.
History
DepositionMay 12, 2014Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 8, 2014Provider: repository / Type: Initial release
Revision 1.1Jan 28, 2015Group: Database references
Revision 2.0Apr 4, 2018Group: Atomic model / Data collection / Category: atom_site / diffrn_source
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_atom_id / _atom_site.label_atom_id / _diffrn_source.type
Revision 2.1May 8, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / 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: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
B: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
C: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
D: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)165,0678
Polymers163,5054
Non-polymers1,5624
Water7,981443
1
B: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
C: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)82,5334
Polymers81,7532
Non-polymers7812
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2730 Å2
ΔGint-10.5 kcal/mol
Surface area28760 Å2
MethodPISA
2
A: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
D: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)82,5334
Polymers81,7532
Non-polymers7812
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2400 Å2
ΔGint-9.9 kcal/mol
Surface area28750 Å2
MethodPISA
Unit cell
Length a, b, c (Å)66.284, 76.026, 78.596
Angle α, β, γ (deg.)85.86, 69.87, 90.17
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein
MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE / HMELK / PROTEIN KINASE EG3 / PEG3 KINASE / PROTEIN KINASE PK38 / HPK38 / TYROSINE-PROTEIN KINASE MELK / MELK


Mass: 40876.273 Da / Num. of mol.: 4 / Fragment: RESIDUES 1-336 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Description: IMAGE CLONE / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: Q14680, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-6Z7 / 7-({4-[(3-hydroxy-5-methoxyphenyl)amino]benzoyl}amino)-1,2,3,4-tetrahydroisoquinolinium


Mass: 390.455 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C23H24N3O3
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 443 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsHIS TAG ADDED AND C-TERMINAL RESIDUES NOT INCLUDED (304)

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.26 Å3/Da / Density % sol: 46 % / Description: NONE

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E / Wavelength: 1.5418
DetectorType: RIGAKU SATURN / Detector: CCD / Date: Jul 30, 2009 / Details: MIRRORS
RadiationMonochromator: NI FILTER / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.55→48 Å / Num. obs: 46777 / % possible obs: 84.8 % / Observed criterion σ(I): 0.75 / Redundancy: 1.72 % / Biso Wilson estimate: 80.44 Å2 / Rmerge(I) obs: 0.07 / Net I/σ(I): 5.5

-
Processing

Software
NameVersionClassification
BUSTER2.11.5refinement
d*TREKdata reduction
d*TREKdata scaling
RefinementMethod to determine structure: OTHER
Starting model: NONE

Resolution: 2.55→41.03 Å / Cor.coef. Fo:Fc: 0.933 / Cor.coef. Fo:Fc free: 0.8814 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.425
Details: IDEAL-DIST CONTACT TERM CONTACT SETUP. ALL ATOMSHAVE CCP4 ATOM TYPE FROM LIBRARY. U VALUES WITH TLS ADDED. THE TEMPERATURE FACTORS OF PARTS OF THIS MODEL ARE VERY HIGH, AND SOME PARTS OF THE ...Details: IDEAL-DIST CONTACT TERM CONTACT SETUP. ALL ATOMSHAVE CCP4 ATOM TYPE FROM LIBRARY. U VALUES WITH TLS ADDED. THE TEMPERATURE FACTORS OF PARTS OF THIS MODEL ARE VERY HIGH, AND SOME PARTS OF THE MOLECULE ARE OBVIOUSLY MOBILE
RfactorNum. reflection% reflectionSelection details
Rfree0.3117 2000 5.04 %RANDOM
Rwork0.2336 ---
obs0.2375 39674 84.8 %-
Displacement parametersBiso mean: 77.559 Å2
Baniso -1Baniso -2Baniso -3
1-3.791 Å2-1.2575 Å2-5.4122 Å2
2--6.7678 Å2-1.7976 Å2
3----10.5587 Å2
Refine analyzeLuzzati coordinate error obs: 0.475 Å
Refinement stepCycle: LAST / Resolution: 2.55→41.03 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10281 0 116 443 10840
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.01110746HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.1414598HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d3763SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes252HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1555HARMONIC16
X-RAY DIFFRACTIONt_it10746HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion6.28
X-RAY DIFFRACTIONt_other_torsion21.72
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1332SEMIHARMONIC5
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_contact11591SEMIHARMONIC4
LS refinement shellResolution: 2.55→2.62 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2995 149 5.11 %
Rwork0.2531 2768 -
all0.2556 2917 -
obs--84.8 %
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)
13.9344-0.0128-2.12891.5035-0.60437.97390.03870.61060.23950.0892-0.002-0.3247-0.17820.152-0.0367-0.22490.15820.02460.05160.0843-0.19358.9821-0.3281-12.2617
25.6633-2.015-0.40243.27940.0341.6807-0.0455-0.2790.24330.2090.1090.0853-0.0887-0.0712-0.0634-0.05670.07820.0276-0.1147-0.0112-0.3021-11.2524.27086.0748
32.6882-3.52370.57381.6756-1.65243.5581-0.0462-0.2376-0.1030.0695-0.1899-0.18010.13090.34780.2361-0.1930.18950.03120.11660.0771-0.108819.6108-11.6699-0.6954
45.11371.3512-3.11814.4103-2.60137.2632-0.17720.3947-0.0568-0.26680.3566-0.1965-0.1791-0.1075-0.1794-0.2315-0.0111-0.043-0.042-0.0356-0.1963-2.9118-34.0453-20.9952
53.63250.517-1.18692.739-0.49274.0774-0.0165-0.10730.10250.26850.19930.256-0.0536-0.0589-0.1829-0.18980.1046-0.0056-0.1655-0.0138-0.1669-23.0125-35.2966-2.4252
61.8158-1.76992.90930.73570.47722.6917-0.0396-0.2441-0.09380.08950.05810.0577-0.00550.296-0.0185-0.3099-0.0489-0.02230.31320.1456-0.102811.1213-40.0866-8.6762
75.0672-0.36-3.1311.42421.44396.5317-0.0562-0.6543-0.1993-0.21340.27920.22270.0189-0.1694-0.223-0.2915-0.09990.00320.07640.055-0.1602-27.1231-38.9375-30.4634
88.5243.2113-0.79664.2311-0.05652.30260.09830.50520.1096-0.21950.1004-0.0716-0.12960.1573-0.1987-0.1158-0.0157-0.0421-0.2554-0.08-0.2853-6.7958-33.2213-49.0315
9-0.79573.0144-0.88610.18070.11612.5712-0.08270.2593-0.1347-0.0608-0.03020.00030.1172-0.3050.113-0.0729-0.1582-0.1339-0.0236-0.1080.0312-37.7408-49.0694-42.9759
106.4151-1.8138-2.51433.57264.05558.8331-0.155-0.5972-0.08890.18570.15930.4907-0.2318-0.0204-0.0043-0.2110.11930.05530.0390.003-0.3499-15.1124.114-22.5398
114.7336-0.4184-1.74352.40851.15564.85930.02220.06970.402-0.3790.1359-0.1814-0.36480.2447-0.158-0.1343-0.02140.01-0.1951-0.0351-0.25845.0053.1388-40.9634
123.45531.0783.2180.43320.6423.7805-0.10040.1862-0.1401-0.1508-0.01760.1495-0.0609-0.25010.118-0.39030.0803-0.07020.2647-0.1839-0.0544-28.6116-1.8675-34.4324
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|1 - A|91 }
2X-RAY DIFFRACTION2{ A|92 - A|274 }
3X-RAY DIFFRACTION3{ A|275 - A|333 }
4X-RAY DIFFRACTION4{ B|1 - B|91 }
5X-RAY DIFFRACTION5{ B|92 - B|274 }
6X-RAY DIFFRACTION6{ B|275 - B|333 }
7X-RAY DIFFRACTION7{ C|0 - C|91 }
8X-RAY DIFFRACTION8{ C|92 - C|274 }
9X-RAY DIFFRACTION9{ C|275 - C|333 }
10X-RAY DIFFRACTION10{ D|1 - D|91 }
11X-RAY DIFFRACTION11{ D|92 - D|274 }
12X-RAY DIFFRACTION12{ D|275 - D|333 }

+
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