[English] 日本語
Yorodumi
- PDB-7juz: Crystal Structure of KSR1:MEK1 in complex with AMP-PNP, and allos... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7juz
TitleCrystal Structure of KSR1:MEK1 in complex with AMP-PNP, and allosteric MEK inhibitor Selumetinib
Components
  • Dual specificity mitogen-activated protein kinase kinase 1
  • Kinase suppressor of Ras 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Kinase / Pseudokinase / drug target / cell signaling and cancer / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


regulation of MAP kinase activity / mitogen-activated protein kinase kinase / MAP-kinase scaffold activity / regulation of Golgi inheritance / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / MAP kinase kinase activity / 14-3-3 protein binding / RAF activation / Signaling by high-kinase activity BRAF mutants ...regulation of MAP kinase activity / mitogen-activated protein kinase kinase / MAP-kinase scaffold activity / regulation of Golgi inheritance / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / MAP kinase kinase activity / 14-3-3 protein binding / RAF activation / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / ruffle membrane / Negative regulation of MAPK pathway / 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 / Signaling by BRAF and RAF1 fusions / late endosome / regulation of cell population proliferation / protein tyrosine kinase activity / Ras protein signal transduction / early endosome / protein kinase activity / non-specific serine/threonine protein kinase / positive regulation of MAPK cascade / protein serine kinase activity / focal adhesion / intracellular membrane-bounded organelle / protein serine/threonine kinase activity / centrosome / endoplasmic reticulum membrane / endoplasmic reticulum / protein-containing complex / mitochondrion / zinc ion binding / ATP binding / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
Kinase suppressor RAS 1, N-terminal helical hairpin / Kinase suppressor RAS 1, N-terminal helical hairpin superfamily / Kinase suppressor RAS 1 N-terminal helical hairpin / : / : / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / C1-like domain superfamily ...Kinase suppressor RAS 1, N-terminal helical hairpin / Kinase suppressor RAS 1, N-terminal helical hairpin superfamily / Kinase suppressor RAS 1 N-terminal helical hairpin / : / : / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / C1-like domain superfamily / Sterile alpha motif/pointed domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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
Similarity search - Domain/homology
Chem-3EW / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / Dual specificity mitogen-activated protein kinase kinase 1 / Kinase suppressor of Ras 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Oryctolagus cuniculus (rabbit)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.21 Å
AuthorsKhan, Z.M. / Dar, A.C.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS)5R01CA227636-02 United States
National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS)1DP2CA186570-01 United States
CitationJournal: Nature / Year: 2020
Title: Structural basis for the action of the drug trametinib at KSR-bound MEK.
Authors: Khan, Z.M. / Real, A.M. / Marsiglia, W.M. / Chow, A. / Duffy, M.E. / Yerabolu, J.R. / Scopton, A.P. / Dar, A.C.
History
DepositionAug 20, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 30, 2020Provider: repository / Type: Initial release
Revision 2.0Oct 7, 2020Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Polymer sequence / Source and taxonomy / Structure summary
Category: atom_site / entity ...atom_site / entity / entity_name_com / entity_poly / entity_poly_seq / entity_src_gen / pdbx_entity_nonpoly / pdbx_entry_details / pdbx_nonpoly_scheme / pdbx_poly_seq_scheme / pdbx_struct_assembly_gen / pdbx_struct_sheet_hbond / pdbx_unobs_or_zero_occ_residues / pdbx_validate_polymer_linkage / pdbx_validate_torsion / struct_asym / struct_conf / struct_mon_prot_cis / struct_ref / struct_ref_seq / struct_ref_seq_dif / struct_sheet_range / struct_site / struct_site_gen
Item: _atom_site.auth_asym_id / _atom_site.label_asym_id ..._atom_site.auth_asym_id / _atom_site.label_asym_id / _atom_site.label_entity_id / _atom_site.label_seq_id / _entity_name_com.entity_id / _entity_poly_seq.entity_id / _entity_poly_seq.num / _pdbx_entity_nonpoly.entity_id / _pdbx_entry_details.compound_details / _pdbx_nonpoly_scheme.asym_id / _pdbx_nonpoly_scheme.entity_id / _pdbx_nonpoly_scheme.pdb_strand_id / _pdbx_poly_seq_scheme.asym_id / _pdbx_poly_seq_scheme.entity_id / _pdbx_poly_seq_scheme.ndb_seq_num / _pdbx_poly_seq_scheme.pdb_strand_id / _pdbx_poly_seq_scheme.seq_id / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_sheet_hbond.range_1_auth_asym_id / _pdbx_struct_sheet_hbond.range_1_label_asym_id / _pdbx_struct_sheet_hbond.range_1_label_seq_id / _pdbx_struct_sheet_hbond.range_2_auth_asym_id / _pdbx_struct_sheet_hbond.range_2_label_asym_id / _pdbx_struct_sheet_hbond.range_2_label_seq_id / _pdbx_unobs_or_zero_occ_residues.auth_asym_id / _pdbx_unobs_or_zero_occ_residues.label_asym_id / _pdbx_unobs_or_zero_occ_residues.label_seq_id / _pdbx_validate_torsion.auth_asym_id / _struct_conf.beg_auth_asym_id / _struct_conf.beg_label_asym_id / _struct_conf.beg_label_seq_id / _struct_conf.end_auth_asym_id / _struct_conf.end_label_asym_id / _struct_conf.end_label_seq_id / _struct_mon_prot_cis.auth_asym_id / _struct_mon_prot_cis.label_asym_id / _struct_mon_prot_cis.label_seq_id / _struct_mon_prot_cis.pdbx_auth_asym_id_2 / _struct_mon_prot_cis.pdbx_label_asym_id_2 / _struct_mon_prot_cis.pdbx_label_seq_id_2 / _struct_ref_seq_dif.align_id / _struct_ref_seq_dif.pdbx_pdb_strand_id / _struct_ref_seq_dif.seq_num / _struct_sheet_range.beg_auth_asym_id / _struct_sheet_range.beg_label_asym_id / _struct_sheet_range.beg_label_seq_id / _struct_sheet_range.end_auth_asym_id / _struct_sheet_range.end_label_asym_id / _struct_sheet_range.end_label_seq_id / _struct_site.details / _struct_site.pdbx_auth_asym_id / _struct_site_gen.auth_asym_id / _struct_site_gen.label_asym_id / _struct_site_gen.label_seq_id
Revision 2.1Dec 30, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 2.2Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Kinase suppressor of Ras 1
C: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,1875
Polymers81,7172
Non-polymers1,4703
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, The MEK1:KSR1 heterodimer was also eluted as a homo-dimer of MEK1:KSR1 heterodimer, centered around KSR1
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5920 Å2
ΔGint-27 kcal/mol
Surface area27180 Å2
MethodPISA
Unit cell
Length a, b, c (Å)136.400, 136.400, 216.600
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number178
Space group name H-MP6122

-
Components

#1: Protein Kinase suppressor of Ras 1


Mass: 38597.137 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KSR1, KSR / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q8IVT5, non-specific serine/threonine protein kinase
#2: Protein Dual specificity mitogen-activated protein kinase kinase 1 / MAPKK 1 / ERK activator kinase 1 / MAPK/ERK kinase 1 / MEK 1


Mass: 43119.371 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Gene: MAP2K1, MEK1, PRKMK1 / Plasmid: pFastBac Dual / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P29678, mitogen-activated protein kinase kinase
#3: Chemical ChemComp-ANP / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER


Mass: 506.196 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H17N6O12P3 / Feature type: SUBJECT OF INVESTIGATION / References: UniProt: P29678*PLUS / Comment: AMP-PNP, energy-carrying molecule analogue*YM
#4: Chemical ChemComp-3EW / 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide


Mass: 457.681 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H15BrClFN4O3 / Feature type: SUBJECT OF INVESTIGATION / Comment: medication*YM
Compound detailsThe author states that kinase suppressor of Ras 1 chain B is proteolytically cleaved between Trp632 ...The author states that kinase suppressor of Ras 1 chain B is proteolytically cleaved between Trp632 and His633.
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.56 Å3/Da / Density % sol: 65.44 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: PEG 2000, MES, pH 6.5, Magnesium acetate

-
Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.2.1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 13, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.21→50 Å / Num. obs: 20371 / % possible obs: 99.8 % / Redundancy: 10.59 % / CC1/2: 1 / Net I/σ(I): 20.99
Reflection shellResolution: 3.21→3.29 Å / Num. unique obs: 1458 / CC1/2: 0.542

-
Processing

Software
NameVersionClassification
PHENIX(1.14rc1_3177)refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2Y4I

2y4i


Resolution: 3.21→49.224 Å / SU ML: 0.45 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 30.66 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2718 1047 5.14 %
Rwork0.2537 --
obs0.2546 20359 99.09 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.21→49.224 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4628 0 89 0 4717
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0044823
X-RAY DIFFRACTIONf_angle_d0.676514
X-RAY DIFFRACTIONf_dihedral_angle_d9.0212884
X-RAY DIFFRACTIONf_chiral_restr0.041705
X-RAY DIFFRACTIONf_plane_restr0.005820
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.21-3.35570.37721350.35172566X-RAY DIFFRACTION95
3.3557-3.56590.351420.31642726X-RAY DIFFRACTION100
3.5659-3.84120.31531420.29242728X-RAY DIFFRACTION100
3.8412-4.22750.29861680.26162734X-RAY DIFFRACTION100
4.2275-4.83880.24581630.24582766X-RAY DIFFRACTION100
4.8388-6.09460.29151520.28072804X-RAY DIFFRACTION100
6.0946-49.2240.23811450.21612988X-RAY DIFFRACTION99

+
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