[English] 日本語
Yorodumi
- PDB-4d2t: Structure of MELK in complex with inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4d2t
TitleStructure of MELK in complex with inhibitors
ComponentsMATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
KeywordsTRANSFERASE / FRAGMENT BASED DRUG DESIGN / KINASE
Function / homology
Function and homology information


neural precursor cell proliferation / intrinsic apoptotic signaling pathway in response to oxidative stress / hemopoiesis / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / G2/M transition of mitotic cell cycle / cell cortex / protein autophosphorylation / cell population proliferation / non-specific serine/threonine protein kinase ...neural precursor cell proliferation / intrinsic apoptotic signaling pathway in response to oxidative stress / hemopoiesis / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / G2/M transition of mitotic cell cycle / cell cortex / protein autophosphorylation / cell population proliferation / non-specific serine/threonine protein kinase / positive regulation of apoptotic process / protein serine kinase activity / protein serine/threonine kinase activity / lipid binding / calcium ion binding / apoptotic process / ATP binding / membrane / plasma membrane / cytoplasm
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-3I7 / Maternal embryonic leucine zipper kinase
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / OTHER / Resolution: 2.7 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 13, 2014Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 15, 2014Provider: repository / Type: Initial release
Revision 1.1Jan 28, 2015Group: Database references
Revision 1.2Mar 18, 2015Group: Refinement description
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)164,8558
Polymers163,5054
Non-polymers1,3504
Water7,134396
1
A: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,2142
Polymers40,8761
Non-polymers3371
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
C: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,2142
Polymers40,8761
Non-polymers3371
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
B: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,2142
Polymers40,8761
Non-polymers3371
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,2142
Polymers40,8761
Non-polymers3371
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)66.526, 75.410, 79.736
Angle α, β, γ (deg.)86.03, 69.05, 90.03
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 ...HMELK / PROTEIN KINASE EG3 / PEG3 KINASE / PROTEIN KINASE PK38 / HPK38 / TYROSINE-PROTEIN KINASE MELK / 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, non-specific protein-tyrosine kinase
#2: Chemical
ChemComp-3I7 / 3-[2-(phenylcarbamoyl)-5-(1H-pyrazol-4-yl)phenoxy]propan-1-aminium


Mass: 337.396 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C19H21N4O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 396 / 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: Sep 22, 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: 2.7→48.5 Å / Num. obs: 39601 / % possible obs: 93.1 % / Observed criterion σ(I): 0.75 / Redundancy: 1.9 % / Biso Wilson estimate: 84.38 Å2 / Rmerge(I) obs: 0.07 / Net I/σ(I): 5.9

-
Processing

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

Resolution: 2.7→48.54 Å / Cor.coef. Fo:Fc: 0.9147 / Cor.coef. Fo:Fc free: 0.8563 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.491
RfactorNum. reflection% reflectionSelection details
Rfree0.34 1870 5.07 %RANDOM
Rwork0.2696 ---
obs0.2732 36893 93.14 %-
Displacement parametersBiso mean: 89.482 Å2
Baniso -1Baniso -2Baniso -3
1-8.5337 Å2-1.9684 Å2-7.7593 Å2
2---2.6209 Å2-0.6359 Å2
3----5.9128 Å2
Refine analyzeLuzzati coordinate error obs: 0.674 Å
Refinement stepCycle: LAST / Resolution: 2.7→48.54 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10279 0 100 396 10775
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0110706HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.1114533HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d3741SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes253HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1550HARMONIC16
X-RAY DIFFRACTIONt_it10706HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion6
X-RAY DIFFRACTIONt_other_torsion22.59
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1335SEMIHARMONIC5
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_contact11861SEMIHARMONIC4
LS refinement shellResolution: 2.7→2.78 Å / Total num. of bins used: 18
RfactorNum. reflection% reflection
Rfree0.3179 123 5.19 %
Rwork0.2469 2249 -
all0.2504 2372 -
obs--93.14 %
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)
14.6932-0.0875-3.61140.81610.08135.3691-0.06070.42070.1113-0.3382-0.0288-0.447-0.1360.28440.0895-0.21190.21170.2134-0.23330.12120.18229.8447-0.1651-11.1599
25.0387-1.0016-1.07387.38770.73482.075-0.0097-0.03350.17270.712-0.10860.33320.0684-0.18970.1183-0.03510.09060.1529-0.3071-0.0454-0.0252-10.70024.27676.6559
33.1165-3.8061-1.51210.4112-1.49274.15710.08710.0210.0240.1689-0.1214-0.14520.22040.26180.0343-0.32290.20.0693-0.25180.12740.315820.4232-11.36440.3483
44.0381-0.5305-2.84295.3384-1.36556.4406-0.05830.1982-0.0584-0.712-0.0025-0.2951-0.18370.15880.0608-0.2580.03040.0754-0.1319-0.0086-0.036-2.533-34.1549-20.737
54.15980.0197-1.74443.2647-1.16235.67840.01970.38490.11770.32130.23850.42-0.3827-0.4792-0.2583-0.27740.15860.0837-0.2861-0.00180.0622-22.6052-35.1702-2.0576
63.2901-1.82833.30260.1345-0.34571.69030.0387-0.1518-0.03930.1213-0.1356-0.07470.06960.23690.0969-0.3383-0.03990.05570.12570.18410.219511.4173-39.2354-8.2652
73.7361-1.0372-3.00021.50210.3535.5646-0.1038-0.3031-0.13130.18680.05360.4993-0.1519-0.2420.0502-0.3178-0.19060.1047-0.308-0.04410.3361-28.0626-37.9995-32.6021
86.57682.1537-1.847.3419-1.18081.05660.12240.21570.5027-0.6849-0.1571-0.27460.11540.23360.03480.13710.01850.1309-0.30260.018-0.0254-7.1326-33.3072-49.7337
91.62043.08940.18320.40091.92210.81410.04830.12210.0935-0.095-0.10280.14270.0807-0.16050.0546-0.0419-0.1935-0.0479-0.3061-0.05220.2731-38.4184-48.838-44.2353
104.9058-0.956-2.29144.98522.37148.1765-0.0507-0.6396-0.08830.63920.02270.1559-0.061-0.17290.028-0.28620.01520.0651-0.1136-0.0177-0.048-15.29613.738-22.9576
115.9254-0.3828-3.35013.37190.66517.08150.0327-0.3330.3573-0.37230.1404-0.4543-0.3960.5711-0.1731-0.2771-0.07740.101-0.3189-0.0710.04054.39873.044-41.2053
122.12613.2982.46431.30920.32372.4631-0.00150.03730.0015-0.0349-0.08680.28770.045-0.40970.0883-0.33450.01220.06980.2831-0.16780.2904-28.9288-1.8508-34.8958
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1CHAIN A AND RESIDUES 1 TO 91
2X-RAY DIFFRACTION2CHAIN A AND RESIDUES 92 TO 274
3X-RAY DIFFRACTION3CHAIN A AND RESIDUES 275 TO 333
4X-RAY DIFFRACTION4CHAIN B AND RESIDUES 0 TO 91
5X-RAY DIFFRACTION5CHAIN B AND RESIDUES 92 TO 274
6X-RAY DIFFRACTION6CHAIN B AND RESIDUES 275 TO 333
7X-RAY DIFFRACTION7CHAIN C AND RESIDUES 1 TO 91
8X-RAY DIFFRACTION8CHAIN C AND RESIDUES 92 TO 274
9X-RAY DIFFRACTION9CHAIN C AND RESIDUES 275 TO 333
10X-RAY DIFFRACTION10CHAIN D AND RESIDUES 3 TO 91
11X-RAY DIFFRACTION11CHAIN D AND RESIDUES 92 TO 274
12X-RAY DIFFRACTION12CHAIN D AND RESIDUES 275 TO 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