[English] 日本語
Yorodumi
- PDB-7m0x: Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7m0x
TitleCrystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and PD0325901
Components
  • Dual specificity mitogen-activated protein kinase kinase 1
  • Serine/threonine-protein kinase B-raf
KeywordsTRANSFERASE / BRAF / MEK1
Function / homology
Function and homology information


epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / negative regulation of homotypic cell-cell adhesion / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / regulation of vascular associated smooth muscle contraction / positive regulation of axon regeneration / CD4-positive, alpha-beta T cell differentiation / mitogen-activated protein kinase kinase / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / Golgi inheritance ...epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / negative regulation of homotypic cell-cell adhesion / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / regulation of vascular associated smooth muscle contraction / positive regulation of axon regeneration / CD4-positive, alpha-beta T cell differentiation / mitogen-activated protein kinase kinase / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / Golgi inheritance / placenta blood vessel development / negative regulation of synaptic vesicle exocytosis / MAP-kinase scaffold activity / positive regulation of muscle contraction / regulation of axon regeneration / cerebellar cortex formation / Signalling to p38 via RIT and RIN / labyrinthine layer development / melanosome transport / head morphogenesis / ARMS-mediated activation / type B pancreatic cell proliferation / endothelial cell apoptotic process / myeloid progenitor cell differentiation / Signaling by MAP2K mutants / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / positive regulation of D-glucose transmembrane transport / negative regulation of fibroblast migration / vesicle transport along microtubule / establishment of protein localization to membrane / positive regulation of axonogenesis / positive regulation of Ras protein signal transduction / regulation of Golgi inheritance / mitogen-activated protein kinase kinase kinase binding / central nervous system neuron differentiation / regulation of T cell differentiation / triglyceride homeostasis / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / Frs2-mediated activation / stress fiber assembly / MAPK3 (ERK1) activation / ERBB2-ERBB3 signaling pathway / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / face development / endodermal cell differentiation / MAP kinase kinase activity / Bergmann glial cell differentiation / positive regulation of ATP biosynthetic process / thyroid gland development / Uptake and function of anthrax toxins / synaptic vesicle exocytosis / positive regulation of protein serine/threonine kinase activity / somatic stem cell population maintenance / protein kinase activator activity / positive regulation of peptidyl-serine phosphorylation / MAP kinase kinase kinase activity / postsynaptic modulation of chemical synaptic transmission / negative regulation of endothelial cell apoptotic process / Schwann cell development / response to axon injury / keratinocyte differentiation / positive regulation of stress fiber assembly / neuron projection morphogenesis / ERK1 and ERK2 cascade / myelination / positive regulation of substrate adhesion-dependent cell spreading / protein serine/threonine/tyrosine kinase activity / positive regulation of autophagy / substrate adhesion-dependent cell spreading / dendrite cytoplasm / insulin-like growth factor receptor signaling pathway / cellular response to calcium ion / response to glucocorticoid / MAP3K8 (TPL2)-dependent MAPK1/3 activation / thymus development / animal organ morphogenesis / protein serine/threonine kinase activator activity / Signal transduction by L1 / cell motility / positive regulation of transcription elongation by RNA polymerase II / Spry regulation of FGF signaling / RAF activation / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / visual learning / small GTPase binding / centriolar satellite / cellular response to xenobiotic stimulus / epidermal growth factor receptor signaling pathway / long-term synaptic potentiation / neuron differentiation / chemotaxis / 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
Similarity search - Function
: / Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. ...: / Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / 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 / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ubiquitin-like domain superfamily / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-4BM / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / Serine/threonine-protein kinase B-raf / Dual specificity mitogen-activated protein kinase kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.47 Å
AuthorsLi, K. / Gonzalez Del-Pino, G. / Ha, B.H. / Park, E. / Eck, M.J.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)P50 CA165962 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R50 CA221830 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R35 CA242461 United States
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2021
Title: Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation.
Authors: Gonzalez-Del Pino, G.L. / Li, K. / Park, E. / Schmoker, A.M. / Ha, B.H. / Eck, M.J.
History
DepositionMar 11, 2021Deposition site: RCSB / Processing site: RCSB
SupersessionApr 21, 2021ID: 6V2V
Revision 1.0Apr 21, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 3, 2021Group: Database references / Category: citation / citation_author / database_2
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Nov 10, 2021Group: Database references / Category: citation / citation_author / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.3Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase B-raf
B: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,84312
Polymers75,8882
Non-polymers1,95510
Water3,081171
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5680 Å2
ΔGint-68 kcal/mol
Surface area25080 Å2
MethodPISA
Unit cell
Length a, b, c (Å)116.527, 116.527, 130.712
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121
Space group name HallP312"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+1/3
#3: -x+y,-x,z+2/3
#4: x-y,-y,-z+2/3
#5: -x,-x+y,-z+1/3
#6: y,x,-z

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein Serine/threonine-protein kinase B-raf / Proto-oncogene B-Raf / p94 / v-Raf murine sarcoma viral oncogene homolog B1


Mass: 32098.104 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Plasmid: pFastBac Dual / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P15056, non-specific serine/threonine protein kinase
#2: Protein Dual specificity mitogen-activated protein kinase kinase 1 / MKK1 / ERK activator kinase 1 / MAPK/ERK kinase 1 / MEK 1


Mass: 43790.281 Da / Num. of mol.: 1 / Mutation: S218A, S222A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP2K1, MEK1, PRKMK1 / Plasmid: pFastBac Dual / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q02750, mitogen-activated protein kinase kinase

-
Non-polymers , 7 types, 181 molecules

#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 / Comment: AMP-PNP, energy-carrying molecule analogue*YM
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#6: Chemical ChemComp-4BM / N-{[(2R)-2,3-dihydroxypropyl]oxy}-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide


Mass: 482.193 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H14F3IN2O4 / Feature type: SUBJECT OF INVESTIGATION
#7: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#8: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 171 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.38 Å3/Da / Density % sol: 63.56 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.4
Details: 100 mM Bis-Tris pH 6.4, 200 mM Ammonium Sulfate, and 22% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.978 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 11, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.978 Å / Relative weight: 1
ReflectionResolution: 2.47→43.571 Å / Num. obs: 37262 / % possible obs: 99.94 % / Redundancy: 19.8 % / Biso Wilson estimate: 45.12 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.179 / Rpim(I) all: 0.0411 / Rrim(I) all: 0.184 / Net I/σ(I): 14.8
Reflection shellResolution: 2.47→2.56 Å / Mean I/σ(I) obs: 2 / Num. unique obs: 3669 / CC1/2: 0.717 / Rpim(I) all: 0.459

-
Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6PP9

6pp9


Resolution: 2.47→43.57 Å / SU ML: 0.2679 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 21.4072
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2151 1906 5.12 %
Rwork0.1781 35352 -
obs0.18 37258 99.96 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 48.58 Å2
Refinement stepCycle: LAST / Resolution: 2.47→43.57 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4654 0 113 171 4938
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0094883
X-RAY DIFFRACTIONf_angle_d1.04736605
X-RAY DIFFRACTIONf_chiral_restr0.0563725
X-RAY DIFFRACTIONf_plane_restr0.0069831
X-RAY DIFFRACTIONf_dihedral_angle_d20.42461845
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.47-2.530.31261570.23382466X-RAY DIFFRACTION100
2.53-2.60.23931280.21982471X-RAY DIFFRACTION100
2.6-2.680.26621350.22462512X-RAY DIFFRACTION100
2.68-2.760.26711560.21222477X-RAY DIFFRACTION100
2.76-2.860.27331260.21432500X-RAY DIFFRACTION99.92
2.86-2.980.21761520.20492499X-RAY DIFFRACTION100
2.98-3.110.25011290.20412498X-RAY DIFFRACTION100
3.11-3.280.26351270.1862514X-RAY DIFFRACTION99.96
3.28-3.480.24721050.18112561X-RAY DIFFRACTION99.96
3.48-3.750.22391230.17452540X-RAY DIFFRACTION100
3.75-4.130.18381520.15322505X-RAY DIFFRACTION100
4.13-4.720.18111360.13932555X-RAY DIFFRACTION99.96
4.72-5.950.1871570.16182561X-RAY DIFFRACTION99.96
5.95-43.570.18641230.18222693X-RAY DIFFRACTION99.79

+
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