[English] 日本語
Yorodumi
- PDB-4xv1: B-Raf Kinase V600E oncogenic mutant in complex with PLX7904 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4xv1
TitleB-Raf Kinase V600E oncogenic mutant in complex with PLX7904
ComponentsSerine/threonine-protein kinase B-raf
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / B-RAF / BRAF / PROTO-ONCOGENE / V600E / KINASE / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
Function / homology
Function and homology information


CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / Signalling to p38 via RIT and RIN / myeloid progenitor cell differentiation / head morphogenesis / ARMS-mediated activation / endothelial cell apoptotic process / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling ...CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / Signalling to p38 via RIT and RIN / myeloid progenitor cell differentiation / head morphogenesis / ARMS-mediated activation / endothelial cell apoptotic process / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / negative regulation of fibroblast migration / positive regulation of D-glucose transmembrane transport / establishment of protein localization to membrane / positive regulation of axonogenesis / regulation of T cell differentiation / mitogen-activated protein kinase kinase binding / Negative feedback regulation of MAPK pathway / Frs2-mediated activation / positive regulation of axon regeneration / stress fiber assembly / face development / MAP kinase kinase activity / synaptic vesicle exocytosis / thyroid gland development / somatic stem cell population maintenance / MAP kinase kinase kinase activity / postsynaptic modulation of chemical synaptic transmission / negative regulation of endothelial cell apoptotic process / response to cAMP / positive regulation of peptidyl-serine phosphorylation / positive regulation of stress fiber assembly / positive regulation of substrate adhesion-dependent cell spreading / ERK1 and ERK2 cascade / substrate adhesion-dependent cell spreading / cellular response to calcium ion / thymus development / animal organ morphogenesis / RAF activation / cellular response to nerve growth factor stimulus / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / visual learning / response to peptide hormone / centriolar satellite / long-term synaptic potentiation / epidermal growth factor receptor signaling pathway / Signaling by RAF1 mutants / Negative regulation of MAPK pathway / 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 / MAPK cascade / cellular response to xenobiotic stimulus / presynapse / T cell receptor signaling pathway / regulation of cell population proliferation / T cell differentiation in thymus / cell body / scaffold protein binding / negative regulation of neuron apoptotic process / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / positive regulation of ERK1 and ERK2 cascade / non-specific serine/threonine protein kinase / postsynapse / protein kinase activity / neuron projection / ciliary basal body / cilium / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / intracellular membrane-bounded organelle / calcium ion binding / positive regulation of gene expression / protein-containing complex binding / negative regulation of apoptotic process / glutamatergic synapse / mitochondrion / zinc ion binding
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. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) ...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. / 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-904 / Serine/threonine-protein kinase B-raf
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.47 Å
AuthorsZhang, Y. / Zhang, C.
CitationJournal: Nature / Year: 2015
Title: RAF inhibitors that evade paradoxical MAPK pathway activation.
Authors: Zhang, C. / Spevak, W. / Zhang, Y. / Burton, E.A. / Ma, Y. / Habets, G. / Zhang, J. / Lin, J. / Ewing, T. / Matusow, B. / Tsang, G. / Marimuthu, A. / Cho, H. / Wu, G. / Wang, W. / Fong, D. / ...Authors: Zhang, C. / Spevak, W. / Zhang, Y. / Burton, E.A. / Ma, Y. / Habets, G. / Zhang, J. / Lin, J. / Ewing, T. / Matusow, B. / Tsang, G. / Marimuthu, A. / Cho, H. / Wu, G. / Wang, W. / Fong, D. / Nguyen, H. / Shi, S. / Womack, P. / Nespi, M. / Shellooe, R. / Carias, H. / Powell, B. / Light, E. / Sanftner, L. / Walters, J. / Tsai, J. / West, B.L. / Visor, G. / Rezaei, H. / Lin, P.S. / Nolop, K. / Ibrahim, P.N. / Hirth, P. / Bollag, G.
History
DepositionJan 26, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 28, 2015Provider: repository / Type: Initial release
Revision 1.1Nov 4, 2015Group: Database references
Revision 1.2Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / diffrn_radiation_wavelength / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase B-raf
B: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,0993
Polymers66,5862
Non-polymers5131
Water72140
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)51.331, 104.817, 110.228
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 33293.133 Da / Num. of mol.: 2 / Fragment: UNP RESIDUES 444-705
Mutation: S446A,S447A,I543A,I544S,I551K,Q562R,L588N,V600E,K630S,F667E,Y673S,A688R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Production host: Escherichia coli (E. coli)
References: UniProt: P15056, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-904 / N'-(3-{[5-(2-cyclopropylpyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl}-2,4-difluorophenyl)-N-ethyl-N-methylsulfuric diamide


Mass: 512.532 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H22F2N6O3S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 40 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.23 Å3/Da / Density % sol: 44.76 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6
Details: 100MM BISTRIS AT PH 6.0, 12.5% 2,5- HEXANEDIOL, 12% PEG3350, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 277K
PH range: 6

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.11587 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 14, 2012
RadiationMonochromator: KHOZU DOUBLE FLAT CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.11587 Å / Relative weight: 1
ReflectionResolution: 2.47→75.958 Å / Num. obs: 22008 / % possible obs: 99.9 % / Observed criterion σ(I): -3 / Redundancy: 5.8 % / Net I/σ(I): 7.8
Reflection shellResolution: 2.47→2.6 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.903 / Mean I/σ(I) obs: 1 / Rsym value: 0.899 / % possible all: 100

-
Processing

Software
NameVersionClassification
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing
PHENIX(PHENIX.REFINE: 1.7.3_928)refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.47→75.958 Å / SU ML: 0.42 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 27.2 / Stereochemistry target values: ENGH & HUBER
RfactorNum. reflection% reflection
Rfree0.273 1128 5.13 %
Rwork0.234 --
obs0.236 22006 99.9 %
Solvent computationShrinkage radii: 0.98 Å / VDW probe radii: 1.2 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 55.83 Å2 / ksol: 0.35 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1-13.8475 Å2-0 Å2-0 Å2
2---2.5562 Å20 Å2
3----11.2913 Å2
Refinement stepCycle: LAST / Resolution: 2.47→75.958 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3912 0 36 40 3988
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0034027
X-RAY DIFFRACTIONf_angle_d0.7235426
X-RAY DIFFRACTIONf_dihedral_angle_d13.91518
X-RAY DIFFRACTIONf_chiral_restr0.054590
X-RAY DIFFRACTIONf_plane_restr0.004686
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.47-2.58250.38361460.35012556X-RAY DIFFRACTION100
2.5825-2.71860.32671300.31542573X-RAY DIFFRACTION100
2.7186-2.8890.31491440.28072545X-RAY DIFFRACTION100
2.889-3.1120.29471410.2562585X-RAY DIFFRACTION100
3.112-3.42520.26561350.23642614X-RAY DIFFRACTION100
3.4252-3.92080.29651460.23372594X-RAY DIFFRACTION100
3.9208-4.93970.22691480.19622624X-RAY DIFFRACTION100
4.9397-75.9580.26091380.21992787X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.51470.11490.21097.69914.1093.7860.04180.0917-0.29390.74530.04120.05880.76450.1122-0.08880.5598-0.01860.03860.35420.02420.2912-1.3023-12.7619-19.4449
24.19382.56690.88565.39112.04084.81920.0781-0.79790.06240.8735-0.28410.01150.9875-0.06560.19920.55460.12340.08270.5481-0.00790.25071.51258.54595.7622
33.87080.76565.57269.54041.0448.0197-0.0842-0.3189-0.05060.186-0.0773-0.0114-0.0346-0.06810.13581.39070.04440.12890.7919-0.19120.63071.7329-2.4522-20.2067
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(CHAIN A AND RESID 449:716 )
2X-RAY DIFFRACTION2(CHAIN B AND RESID 449:721 )
3X-RAY DIFFRACTION3(CHAIN A AND RESID 801:801 )

+
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