[English] 日本語
Yorodumi
- PDB-4ark: CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MAP KINASE KIN... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ark
TitleCRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MAP KINASE KINASE 1 (MEK1) IN COMPLEX WITH A SMALL MOLECULE INHIBITOR AND ADP
ComponentsDUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1
KeywordsTRANSFERASE / KINASE / INHIBITOR
Function / homology
Function and homology information


epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / labyrinthine layer development / type B pancreatic cell proliferation / MAP-kinase scaffold activity / cerebellar cortex formation / Signaling by MAP2K mutants ...epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / labyrinthine layer development / type B pancreatic cell proliferation / MAP-kinase scaffold activity / cerebellar cortex formation / Signaling by MAP2K mutants / regulation of Golgi inheritance / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / positive regulation of axonogenesis / regulation of stress-activated MAPK cascade / Frs2-mediated activation / ERBB2-ERBB3 signaling pathway / protein kinase activator activity / endodermal cell differentiation / face development / MAPK3 (ERK1) activation / Bergmann glial cell differentiation / MAP kinase kinase activity / thyroid gland development / Uptake and function of anthrax toxins / Schwann cell development / keratinocyte differentiation / ERK1 and ERK2 cascade / myelination / protein serine/threonine/tyrosine kinase activity / protein serine/threonine kinase activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / insulin-like growth factor receptor signaling pathway / thymus development / Signal transduction by L1 / cell motility / RAF activation / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / neuron differentiation / positive regulation of protein serine/threonine kinase activity / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / chemotaxis / MAPK cascade / cellular senescence / Signaling by BRAF and RAF1 fusions / late endosome / heart development / scaffold protein binding / protein tyrosine kinase activity / early endosome / positive regulation of ERK1 and ERK2 cascade / protein kinase activity / negative regulation of cell population proliferation / protein phosphorylation / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / centrosome / positive regulation of gene expression / positive regulation of DNA-templated transcription / Golgi apparatus / endoplasmic reticulum / signal transduction / mitochondrion / ATP binding / nucleus / plasma membrane / cytosol
Similarity search - Function
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. ...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
ADENOSINE-5'-DIPHOSPHATE / Chem-M3K / Dual specificity mitogen-activated protein kinase kinase 1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.6 Å
AuthorsHartung, I.V. / Hitchcock, M. / Puehler, F. / Neuhaus, R. / Scholz, A. / Hammer, S. / Petersen, K. / Siemeister, G. / Brittain, D. / Hillig, R.C.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2013
Title: Optimization of Allosteric Mek Inhibitors - Part 1: Venturing Into Unexplored Sar Territories
Authors: Hartung, I.V. / Hitchcock, M. / Puehler, F. / Neuhaus, R. / Scholz, A. / Hammer, S. / Petersen, K. / Siemeister, G. / Brittain, D. / Hillig, R.C.
History
DepositionApr 24, 2012Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 6, 2013Provider: repository / Type: Initial release
Revision 1.1Apr 3, 2013Group: Database references
Revision 1.2Apr 17, 2013Group: Database references
Revision 1.3Dec 14, 2016Group: Data collection
Revision 1.4Dec 20, 2023Group: 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 / pdbx_struct_conn_angle / struct_conn / 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 / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _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 MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,8604
Polymers37,9311
Non-polymers9303
Water86548
1
A: DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1
hetero molecules

A: DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,7218
Polymers75,8612
Non-polymers1,8596
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_665-x+1,-y+1,z1
Buried area3750 Å2
ΔGint-47.2 kcal/mol
Surface area26410 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.411, 82.411, 130.238
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number171
Space group name H-MP62

-
Components

#1: Protein DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1 / MAP KINASE KINASE 1 / MAPKK 1 / MKK1 / ERK ACTIVATOR KINASE 1 / MAPK/ERK KINASE 1 / MEK 1


Mass: 37930.609 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, RESIDUES 62-393
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PQE80L / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / Variant (production host): ARCTIC EXPRESS
References: UniProt: Q02750, mitogen-activated protein kinase kinase
#2: Chemical ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE / Adenosine diphosphate


Mass: 427.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Comment: ADP, energy-carrying molecule*YM
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-M3K / 2-([3R-3,4-dihydroxybutyl]oxy)-4-fluoro-6-[(2-fluoro-4-iodophenyl)amino]benzamide


Mass: 478.229 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H17F2IN2O4
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 48 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsN-TERMINAL M IS CLONING ARTIFACT. LAST EIGHT C-TERMINAL RESIDUES ARE A CLONING ARTIFACT, HEXA HIS ...N-TERMINAL M IS CLONING ARTIFACT. LAST EIGHT C-TERMINAL RESIDUES ARE A CLONING ARTIFACT, HEXA HIS TAG. THIS C- TERMINAL HIS TAG WAS NOT REMOVED BEFORE CRYSTALLIZATION.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.55 Å3/Da / Density % sol: 65.34 % / Description: NONE
Crystal growDetails: 0.1 M IMIDAZOLE-MALATE, 300 MM(NH4)H2PO4, 13% PEG 8000, PH 5.8

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 0.979
DetectorType: ADSC CCD / Detector: CCD / Date: Jul 24, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 2.6→30 Å / Num. obs: 15320 / % possible obs: 99.1 % / Observed criterion σ(I): 0 / Redundancy: 3.6 % / Biso Wilson estimate: 87.17 Å2 / Rmerge(I) obs: 0.1 / Net I/σ(I): 11.9
Reflection shellResolution: 2.6→2.74 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.76 / Mean I/σ(I) obs: 1.7 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.4.0062refinement
MOSFLMdata reduction
SCALAdata scaling
REFMAC5phasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PROTEIN CHAIN OF PDB ENTRY 1S9J

1s9j


Resolution: 2.6→19.8 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.951 / SU B: 16.819 / SU ML: 0.191 / Cross valid method: THROUGHOUT / ESU R: 0.317 / ESU R Free: 0.228 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. LIGAND (M3K) CO-CRYSTALLIZED IN THE PRESENCE OF MG AND ADP AS PUBLISHED FOR THE ATP COMPLEX DESCRIBED IN PDB ENTRY 1S9J.
RfactorNum. reflection% reflectionSelection details
Rfree0.21135 769 5 %RANDOM
Rwork0.17205 ---
obs0.17395 14461 98.83 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 91.152 Å2
Baniso -1Baniso -2Baniso -3
1-1.53 Å20.76 Å20 Å2
2--1.53 Å20 Å2
3----2.29 Å2
Refinement stepCycle: LAST / Resolution: 2.6→19.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2279 0 54 48 2381
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0222382
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.4372.0053216
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7355289
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.32324.44499
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.10515428
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.6351512
X-RAY DIFFRACTIONr_chiral_restr0.10.2351
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0211757
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.69421446
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it2.94332334
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.782936
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it2.863882
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.6→2.66 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.334 59 -
Rwork0.336 1017 -
obs--100 %
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)
15.76372.0090.89327.83932.207910.39190.1477-0.43320.1766-0.0217-0.22230.76690.489-1.13990.0746-0.3319-0.1175-0.03860.2258-0.0577-0.410930.9452751.437
24.55490.13491.16733.05950.39746.13230.09480.07420.6308-0.3209-0.1516-0.4678-0.37760.20530.0568-0.41960.08250.0989-0.0984-0.0222-0.326740.31736.8628.816
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A61 - 119
2X-RAY DIFFRACTION1A128 - 145
3X-RAY DIFFRACTION2A120 - 127
4X-RAY DIFFRACTION2A146 - 382

+
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