[English] 日本語
Yorodumi
- PDB-9o0u: Crystal structure of CRAF/MEK1 complex with PLX4720 and CH5126766 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9o0u
TitleCrystal structure of CRAF/MEK1 complex with PLX4720 and CH5126766
Components
  • Dual specificity mitogen-activated protein kinase kinase 1
  • RAF proto-oncogene serine/threonine-protein kinase
KeywordsTRANSFERASE / CRAF-MEK1 complex / MAPK pathway
Function / homology
Function and homology information


death-inducing signaling complex assembly / 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 / intermediate filament cytoskeleton organization / mitogen-activated protein kinase kinase / Golgi inheritance / placenta blood vessel development ...death-inducing signaling complex assembly / 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 / intermediate filament cytoskeleton organization / mitogen-activated protein kinase kinase / Golgi inheritance / placenta blood vessel development / MAP-kinase scaffold activity / positive regulation of muscle contraction / labyrinthine layer development / regulation of axon regeneration / cerebellar cortex formation / regulation of Rho protein signal transduction / melanosome transport / type B pancreatic cell proliferation / Signaling by MAP2K mutants / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / vesicle transport along microtubule / positive regulation of axonogenesis / positive regulation of Ras protein signal transduction / insulin secretion involved in cellular response to glucose stimulus / regulation of Golgi inheritance / mitogen-activated protein kinase kinase kinase binding / central nervous system neuron differentiation / triglyceride homeostasis / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / IFNG signaling activates MAPKs / regulation of stress-activated MAPK cascade / Frs2-mediated activation / GP1b-IX-V activation signalling / MAPK3 (ERK1) activation / ERBB2-ERBB3 signaling pathway / neurotrophin TRK receptor signaling pathway / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / pseudopodium / endodermal cell differentiation / face development / MAP kinase kinase activity / Bergmann glial cell differentiation / positive regulation of ATP biosynthetic process / regulation of cell differentiation / thyroid gland development / Uptake and function of anthrax toxins / positive regulation of protein serine/threonine kinase activity / extrinsic apoptotic signaling pathway via death domain receptors / somatic stem cell population maintenance / protein kinase activator activity / positive regulation of peptidyl-serine phosphorylation / MAP kinase kinase kinase activity / type II interferon-mediated signaling pathway / negative regulation of protein-containing complex assembly / response to axon injury / Schwann cell development / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / keratinocyte differentiation / neuron projection morphogenesis / response to muscle stretch / ERK1 and ERK2 cascade / myelination / positive regulation of autophagy / protein serine/threonine/tyrosine kinase activity / CD209 (DC-SIGN) signaling / dendrite cytoplasm / insulin-like growth factor receptor signaling pathway / response to glucocorticoid / MAP3K8 (TPL2)-dependent MAPK1/3 activation / thymus development / adenylate cyclase activator activity / protein serine/threonine kinase activator activity / Signal transduction by L1 / cell motility / wound healing / positive regulation of transcription elongation by RNA polymerase II / RAF activation / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / small GTPase binding / Stimuli-sensing channels / 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 / Signaling downstream of RAS mutants / Signaling by BRAF and RAF1 fusions / cellular senescence / insulin receptor signaling pathway / late endosome / MAPK cascade / heart development / response to oxidative stress / protein tyrosine kinase activity
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 / Ubiquitin-like domain superfamily / 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-324 / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / Chem-CHU / RAF proto-oncogene serine/threonine-protein kinase / Dual specificity mitogen-activated protein kinase kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.91 Å
AuthorsJang, D.M. / Eck, M.J.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R35CA242461-06 United States
CitationJournal: J.Biol.Chem. / Year: 2025
Title: Characterization and inhibitor sensitivity of ARAF, BRAF, and CRAF kinases
Authors: Tkacik, E. / Jang, D.M. / Boxer, K. / Ha, B.H. / Eck, M.J.
History
DepositionApr 3, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 15, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: RAF proto-oncogene serine/threonine-protein kinase
B: Dual specificity mitogen-activated protein kinase kinase 1
C: RAF proto-oncogene serine/threonine-protein kinase
D: Dual specificity mitogen-activated protein kinase kinase 1
E: RAF proto-oncogene serine/threonine-protein kinase
F: Dual specificity mitogen-activated protein kinase kinase 1
G: RAF proto-oncogene serine/threonine-protein kinase
H: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)306,37517
Polymers302,3278
Non-polymers4,0479
Water79344
1
A: RAF proto-oncogene serine/threonine-protein kinase
B: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,4674
Polymers75,5822
Non-polymers8852
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: RAF proto-oncogene serine/threonine-protein kinase
D: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,4674
Polymers75,5822
Non-polymers8852
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
E: RAF proto-oncogene serine/threonine-protein kinase
F: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,4674
Polymers75,5822
Non-polymers8852
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
G: RAF proto-oncogene serine/threonine-protein kinase
H: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,9735
Polymers75,5822
Non-polymers1,3913
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)180.990, 180.990, 367.020
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number179
Space group name H-MP6522
Space group name HallP652(x,y,z+1/12)
Symmetry operation#1: x,y,z
#2: x-y,x,z+5/6
#3: y,-x+y,z+1/6
#4: -y,x-y,z+2/3
#5: -x+y,-x,z+1/3
#6: x-y,-y,-z
#7: -x,-x+y,-z+1/3
#8: -x,-y,z+1/2
#9: y,x,-z+2/3
#10: -y,-x,-z+1/6
#11: -x+y,y,-z+1/2
#12: x,x-y,-z+5/6

-
Components

-
Protein , 2 types, 8 molecules ACEGBDFH

#1: Protein
RAF proto-oncogene serine/threonine-protein kinase / Proto-oncogene c-RAF / cRaf / Raf-1


Mass: 32005.803 Da / Num. of mol.: 4 / Mutation: Y340D, Y341D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RAF1, RAF / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P04049, non-specific serine/threonine protein kinase
#2: 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: 43576.039 Da / Num. of mol.: 4 / Mutation: S218A, S222A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP2K1, MEK1, PRKMK1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q02750, mitogen-activated protein kinase kinase

-
Non-polymers , 4 types, 53 molecules

#3: Chemical
ChemComp-324 / N-{3-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide


Mass: 413.826 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Formula: C17H14ClF2N3O3S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-CHU / N-(3-fluoro-4-{[4-methyl-2-oxo-7-(pyrimidin-2-yloxy)-2H-chromen-3-yl]methyl}pyridin-2-yl)-N'-methylsulfuric diamide / CH5126766


Mass: 471.462 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Formula: C21H18FN5O5S / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-ANP / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER


Mass: 506.196 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C10H17N6O12P3 / Feature type: SUBJECT OF INVESTIGATION / Comment: AMP-PNP, energy-carrying molecule analogue*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 44 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.87 Å3/Da / Density % sol: 57.14 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop
Details: 18% PEG 3350, 0.1 M Sodium citrate pH 5.6, 4% Tacsimate pH 5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-1 / Wavelength: 0.9202 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Nov 8, 2024
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9202 Å / Relative weight: 1
ReflectionResolution: 2.91→50 Å / Num. obs: 147338 / % possible obs: 99.7 % / Redundancy: 4.79 % / Biso Wilson estimate: 67.3 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.132 / Net I/σ(I): 9.63
Reflection shellResolution: 2.91→3.08 Å / Redundancy: 4.69 % / Rmerge(I) obs: 1.044 / Num. unique obs: 23539 / CC1/2: 0.995 / % possible all: 98.8

-
Processing

Software
NameVersionClassification
PHENIX1.21.2_5419refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.91→46.1 Å / SU ML: 0.3576 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.7681
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2639 3911 5 %
Rwork0.2302 74312 -
obs0.2318 78223 99.77 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 80.51 Å2
Refinement stepCycle: LAST / Resolution: 2.91→46.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms18472 0 271 44 18787
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.006719159
X-RAY DIFFRACTIONf_angle_d1.086125863
X-RAY DIFFRACTIONf_chiral_restr0.06532819
X-RAY DIFFRACTIONf_plane_restr0.00813282
X-RAY DIFFRACTIONf_dihedral_angle_d15.43367241
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.91-2.940.37251310.35742492X-RAY DIFFRACTION95.17
2.94-2.980.38451380.33492622X-RAY DIFFRACTION100
2.98-3.020.32631370.32242608X-RAY DIFFRACTION100
3.02-3.060.37031380.30642615X-RAY DIFFRACTION100
3.06-3.110.35571370.29172611X-RAY DIFFRACTION100
3.11-3.150.31371370.27522599X-RAY DIFFRACTION100
3.15-3.20.30821380.28172630X-RAY DIFFRACTION100
3.2-3.250.31331380.27872608X-RAY DIFFRACTION100
3.25-3.310.3141380.26962622X-RAY DIFFRACTION100
3.31-3.370.3231380.2822640X-RAY DIFFRACTION100
3.37-3.440.33271380.28162618X-RAY DIFFRACTION100
3.44-3.510.30711380.26832626X-RAY DIFFRACTION100
3.51-3.580.25791390.25432624X-RAY DIFFRACTION100
3.58-3.670.26991380.23582635X-RAY DIFFRACTION100
3.67-3.760.26871390.22642642X-RAY DIFFRACTION100
3.76-3.860.28321400.22722654X-RAY DIFFRACTION100
3.86-3.970.27241390.23332635X-RAY DIFFRACTION100
3.97-4.10.27661390.22512646X-RAY DIFFRACTION100
4.1-4.250.22411400.21262652X-RAY DIFFRACTION100
4.25-4.420.22671400.19482668X-RAY DIFFRACTION99.96
4.42-4.620.21071400.19022658X-RAY DIFFRACTION99.89
4.62-4.860.22631400.19832667X-RAY DIFFRACTION99.86
4.86-5.160.27721410.20872684X-RAY DIFFRACTION99.89
5.16-5.560.26191420.21852685X-RAY DIFFRACTION99.93
5.56-6.120.28481430.2322716X-RAY DIFFRACTION99.97
6.12-70.29141440.23392737X-RAY DIFFRACTION99.93
7-8.810.2281460.19532773X-RAY DIFFRACTION99.97
8.81-46.10.18991550.1932945X-RAY DIFFRACTION99.17

+
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