[English] 日本語
Yorodumi
- PDB-7m0t: Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7m0t
TitleCrystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Selumetinib
Components
  • Dual specificity mitogen-activated protein kinase kinase 1
  • Serine/threonine-protein kinase B-raf
KeywordsTRANSFERASE / BRAF / MEK1
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 / CD4-positive, alpha-beta T cell differentiation / positive regulation of axon regeneration / myeloid progenitor cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / mitogen-activated protein kinase kinase / melanosome transport ...negative regulation of homotypic cell-cell adhesion / regulation of vascular associated smooth muscle contraction / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / CD4-positive, alpha-beta T cell differentiation / positive regulation of axon regeneration / myeloid progenitor cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / mitogen-activated protein kinase kinase / melanosome transport / Golgi inheritance / MAP kinase scaffold activity / Signalling to p38 via RIT and RIN / head morphogenesis / endothelial cell apoptotic process / positive regulation of muscle contraction / ARMS-mediated activation / negative regulation of fibroblast migration / 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 / positive regulation of axonogenesis / vesicle transport along microtubule / regulation of Golgi inheritance / mitogen-activated protein kinase kinase kinase binding / somatic stem cell population maintenance / regulation of T cell differentiation / face development / triglyceride homeostasis / regulation of early endosome to late endosome transport / thyroid gland development / Negative feedback regulation of MAPK pathway / regulation of stress-activated MAPK cascade / Frs2-mediated activation / stress fiber assembly / MAPK3 (ERK1) activation / ERBB2-ERBB3 signaling pathway / positive regulation of protein serine/threonine kinase activity / MAP kinase kinase activity / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / neuromuscular junction development / positive regulation of ATP biosynthetic process / response to axon injury / Uptake and function of anthrax toxins / synaptic vesicle exocytosis / positive regulation of peptidyl-serine phosphorylation / negative regulation of endothelial cell apoptotic process / MAP kinase kinase kinase activity / ERK1 and ERK2 cascade / centriolar satellite / protein kinase activator activity / Schwann cell development / thymus development / postsynaptic modulation of chemical synaptic transmission / positive regulation of stress fiber assembly / substrate adhesion-dependent cell spreading / myelination / neuron projection morphogenesis / positive regulation of substrate adhesion-dependent cell spreading / insulin-like growth factor receptor signaling pathway / protein serine/threonine/tyrosine kinase activity / T cell differentiation in thymus / animal organ morphogenesis / cellular response to calcium ion / positive regulation of autophagy / response to glucocorticoid / dendrite cytoplasm / Signal transduction by L1 / protein serine/threonine kinase activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / sperm principal piece / sperm end piece / cellular response to xenobiotic stimulus / positive regulation of transcription elongation by RNA polymerase II / visual learning / RAF activation / Signaling by high-kinase activity BRAF mutants / Spry regulation of FGF signaling / MAP2K and MAPK activation / cellular senescence / long-term synaptic potentiation / small GTPase binding / epidermal growth factor receptor signaling pathway / chemotaxis / neuron differentiation / sperm midpiece / 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 / regulation of cell population proliferation / T cell receptor signaling pathway / presynapse / 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 / 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
Chem-3EW / 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: 3.19 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: 6V32
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
B: Dual specificity mitogen-activated protein kinase kinase 1
A: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,4077
Polymers75,8882
Non-polymers1,5195
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4570 Å2
ΔGint-34 kcal/mol
Surface area25680 Å2
MethodPISA
Unit cell
Length a, b, c (Å)116.964, 116.964, 129.733
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121

-
Components

#1: 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: PAC8 / Cell line (production host): Sf9 / 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: 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 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P15056, non-specific serine/threonine protein kinase
#3: 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
#4: 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
#5: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
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: 8.5
Details: 100 mM Tris 8.5, 200 mM Lithium Sulfate and 22% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.979 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 13, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 3.19→43.44 Å / Num. obs: 17505 / % possible obs: 99.77 % / Redundancy: 9.8 % / Biso Wilson estimate: 109.82 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.138 / Rpim(I) all: 0.066 / Rrim(I) all: 0.153 / Net I/σ(I): 10.9
Reflection shellResolution: 3.19→3.304 Å / Redundancy: 10 % / Mean I/σ(I) obs: 2 / Num. unique obs: 1733 / CC1/2: 0.743 / Rpim(I) all: 0.605 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.19_4092refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
Aimlessdata scaling
PHASESphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6PP9

6pp9


Resolution: 3.19→43.435 Å / SU ML: 0.53 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 29.55 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2539 804 4.59 %
Rwork0.1965 16700 -
obs0.1991 17504 99.84 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 184.09 Å2 / Biso mean: 102.2845 Å2 / Biso min: 61.41 Å2
Refinement stepCycle: final / Resolution: 3.19→43.435 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4631 0 91 0 4722
Biso mean--100.45 --
Num. residues----584
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 6

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
3.19-3.390.34871420.315127322874100
3.39-3.650.36031380.257127442882100
3.65-4.020.26431320.236327492881100
4.02-4.60.23691430.180927572900100
4.6-5.790.25571260.199428082934100
5.8-43.440.21811230.1592910303399

+
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