[English] 日本語
Yorodumi
- PDB-6u2g: BRAF-MEK complex with AMP-PCP bound to BRAF -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6u2g
TitleBRAF-MEK complex with AMP-PCP bound to BRAF
Components
  • Dual specificity mitogen-activated protein kinase kinase 1
  • Serine/threonine-protein kinase B-raf
KeywordsTRANSFERASE / Kinase / AMP-PCP / dimer / SIGNALING PROTEI
Function / homology
Function and homology information


negative regulation of homotypic cell-cell adhesion / regulation of vascular associated smooth muscle contraction / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / mitogen-activated protein kinase kinase / melanosome transport / Golgi inheritance / MAP kinase scaffold activity / Signalling to p38 via RIT and RIN / positive regulation of muscle contraction / ARMS-mediated activation ...negative regulation of homotypic cell-cell adhesion / regulation of vascular associated smooth muscle contraction / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / mitogen-activated protein kinase kinase / melanosome transport / Golgi inheritance / MAP kinase scaffold activity / Signalling to p38 via RIT and RIN / positive regulation of muscle contraction / ARMS-mediated activation / 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 / establishment of protein localization to membrane / vesicle transport along microtubule / regulation of Golgi inheritance / mitogen-activated protein kinase kinase kinase binding / triglyceride homeostasis / positive regulation of protein serine/threonine kinase activity / regulation of early endosome to late endosome transport / Negative feedback regulation of MAPK pathway / regulation of stress-activated MAPK cascade / Frs2-mediated activation / MAPK3 (ERK1) activation / ERBB2-ERBB3 signaling pathway / MAP kinase kinase activity / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of ATP biosynthetic process / neuromuscular junction development / ERK1 and ERK2 cascade / response to axon injury / Uptake and function of anthrax toxins / positive regulation of peptidyl-serine phosphorylation / MAP kinase kinase kinase activity / protein kinase activator activity / Schwann cell development / postsynaptic modulation of chemical synaptic transmission / myelination / insulin-like growth factor receptor signaling pathway / animal organ morphogenesis / protein serine/threonine/tyrosine kinase activity / cellular response to calcium ion / neuron projection morphogenesis / response to glucocorticoid / positive regulation of autophagy / protein serine/threonine kinase activator activity / dendrite cytoplasm / Signal transduction by L1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / positive regulation of transcription elongation by RNA polymerase II / RAF activation / Signaling by high-kinase activity BRAF mutants / Spry regulation of FGF signaling / MAP2K and MAPK activation / cellular senescence / epidermal growth factor receptor signaling pathway / chemotaxis / small GTPase binding / 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 / MAPK cascade / Negative regulation of MAPK pathway / Signaling by BRAF and RAF1 fusions / late endosome / neuron differentiation / protein tyrosine kinase activity / response to oxidative stress / ciliary basal body / scaffold protein binding / cell body / cell cortex / microtubule / early endosome / perikaryon / positive regulation of ERK1 and ERK2 cascade / protein kinase activity / protein phosphorylation / non-specific serine/threonine protein kinase / postsynapse / postsynaptic density / neuron projection / positive regulation of cell migration / negative regulation of cell population proliferation / negative regulation of gene expression / protein serine kinase activity / axon / focal adhesion / protein serine/threonine kinase activity / centrosome / positive regulation of gene expression / calcium ion binding / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / protein-containing complex binding / perinuclear region of cytoplasm / glutamatergic synapse / Golgi apparatus
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 / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / 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
PHOSPHOMETHYLPHOSPHONIC 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 / molecular replacement / Resolution: 2.886 Å
AuthorsLiau, N.P.D. / Wendorff, T. / Hymowitz, S. / Sudhamsu, J.
CitationJournal: Nat.Struct.Mol.Biol. / Year: 2020
Title: Negative regulation of RAF kinase activity by ATP is overcome by 14-3-3-induced dimerization.
Authors: Liau, N.P.D. / Wendorff, T.J. / Quinn, J.G. / Steffek, M. / Phung, W. / Liu, P. / Tang, J. / Irudayanathan, F.J. / Izadi, S. / Shaw, A.S. / Malek, S. / Hymowitz, S.G. / Sudhamsu, J.
History
DepositionAug 19, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 28, 2019Provider: repository / Type: Initial release
Revision 1.1Feb 5, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Feb 26, 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 1.3Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _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_asym_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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)79,8807
Polymers78,7252
Non-polymers1,1555
Water59433
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4740 Å2
ΔGint-47 kcal/mol
Surface area25390 Å2
MethodPISA
Unit cell
Length a, b, c (Å)117.420, 117.420, 130.273
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein Dual specificity mitogen-activated protein kinase kinase 1 / MKK1 / ERK activator kinase 1 / MAPK/ERK kinase 1 / MEK 1


Mass: 43506.871 Da / Num. of mol.: 1
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
#2: Protein Serine/threonine-protein kinase B-raf / Proto-oncogene B-Raf / p94 / v-Raf murine sarcoma viral oncogene homolog B1


Mass: 35217.633 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P15056, non-specific serine/threonine protein kinase

-
Non-polymers , 4 types, 38 molecules

#3: Chemical ChemComp-ACP / PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / ADENOSINE-5'-[BETA, GAMMA-METHYLENE]TRIPHOSPHATE


Mass: 505.208 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C11H18N5O12P3 / Comment: AMP-PCP, 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-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 33 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.29 Å3/Da / Density % sol: 62.65 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: Ammonium sulfate, MES, PEK 8000

-
Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.99999 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 12, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99999 Å / Relative weight: 1
ReflectionResolution: 2.886→80.159 Å / Num. obs: 23613 / % possible obs: 99.05 % / Redundancy: 2 % / CC1/2: 1 / Rmerge(I) obs: 0.02315 / Net I/av σ(I): 17.85 / Net I/σ(I): 17.85
Reflection shellResolution: 2.886→2.989 Å / Rmerge(I) obs: 0.319 / Mean I/σ(I) obs: 2.08 / Num. unique obs: 2337 / CC1/2: 0.786 / % possible all: 99.96

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
PHENIX1.12-2829_finalrefinement
PHASERphasing
PDB_EXTRACT3.25data extraction
XDSdata reduction
XSCALEdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4MNE

4mne


Resolution: 2.886→80.159 Å / SU ML: 0.41 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 27.48 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2757 1205 5.1 %
Rwork0.229 22403 -
obs0.2313 23608 99.06 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 194.95 Å2 / Biso mean: 79.0371 Å2 / Biso min: 37.2 Å2
Refinement stepCycle: final / Resolution: 2.886→80.159 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4531 0 69 33 4633
Biso mean--63.05 58.16 -
Num. residues----573
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0164703
X-RAY DIFFRACTIONf_angle_d1.3246336
X-RAY DIFFRACTIONf_chiral_restr0.073699
X-RAY DIFFRACTIONf_plane_restr0.008799
X-RAY DIFFRACTIONf_dihedral_angle_d25.8441770
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.886-3.00180.35841490.31142451100
3.0018-3.13840.3091470.26452467100
3.1384-3.30390.29761070.25142507100
3.3039-3.51090.29881220.26952492100
3.5109-3.78190.26281240.2271230992
3.7819-4.16250.24691520.21152469100
4.1625-4.76480.23841260.19832512100
4.7648-6.00280.24021280.22242554100
6.0028-80.1590.31481500.22612642100
Refinement TLS params.Method: refined / Origin x: 52.4199 Å / Origin y: -44.4515 Å / Origin z: -17.9216 Å
111213212223313233
T0.2752 Å2-0.0022 Å2-0.0436 Å2-0.685 Å20.1017 Å2--0.4696 Å2
L0.8237 °20.1389 °20.1809 °2-2.5004 °21.6543 °2--3.486 °2
S0.0735 Å °-0.2028 Å °-0.1438 Å °0.1107 Å °0.0901 Å °-0.1602 Å °-0.0446 Å °-0.1873 Å °-0.0932 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA43 - 902
2X-RAY DIFFRACTION1allB451 - 901
3X-RAY DIFFRACTION1allS1 - 40
4X-RAY DIFFRACTION1allC1

+
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