[English] 日本語
Yorodumi
- PDB-4ksq: Crystal Structure of Human B-raf bound to a DFG-out Inhibitor 5B -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ksq
TitleCrystal Structure of Human B-raf bound to a DFG-out Inhibitor 5B
ComponentsSerine/threonine-protein kinase B-raf
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / human serine/theronine protein Kinase / kinase drug complex / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


trehalose metabolism in response to stress / CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / head morphogenesis / Signalling to p38 via RIT and RIN / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling ...trehalose metabolism in response to stress / CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / head morphogenesis / Signalling to p38 via RIT and RIN / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / endothelial cell apoptotic process / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / mitogen-activated protein kinase kinase binding / regulation of T cell differentiation / Negative feedback regulation of MAPK pathway / positive regulation of axonogenesis / Frs2-mediated activation / stress fiber assembly / positive regulation of axon regeneration / face development / synaptic vesicle exocytosis / somatic stem cell population maintenance / MAP kinase kinase activity / thyroid gland development / MAP kinase kinase kinase activity / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of stress fiber assembly / response to cAMP / ERK1 and ERK2 cascade / cellular response to calcium ion / substrate adhesion-dependent cell spreading / cellular response to nerve growth factor stimulus / thymus development / long-term synaptic potentiation / animal organ morphogenesis / Spry regulation of FGF signaling / RAF activation / Signaling by high-kinase activity BRAF mutants / visual learning / MAP2K and MAPK activation / epidermal growth factor receptor signaling pathway / response to peptide hormone / 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 / MAPK cascade / Signaling by BRAF and RAF1 fusions / cellular response to xenobiotic stimulus / presynapse / cell body / positive regulation of peptidyl-serine phosphorylation / T cell differentiation in thymus / regulation of cell population proliferation / T cell receptor signaling pathway / scaffold protein binding / negative regulation of neuron apoptotic process / positive regulation of ERK1 and ERK2 cascade / non-specific serine/threonine protein kinase / neuron projection / protein kinase activity / protein phosphorylation / protein serine kinase activity / intracellular membrane-bounded organelle / protein serine/threonine kinase activity / calcium ion binding / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / mitochondrion / ATP binding / identical protein binding / nucleus / plasma membrane / cytosol
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) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain ...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 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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-1SW / Serine/threonine-protein kinase B-raf
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.3 Å
AuthorsYano, J.K. / Masanori, O.
CitationJournal: J.Med.Chem. / Year: 2013
Title: Discovery of a Selective Kinase Inhibitor (TAK-632) Targeting Pan-RAF Inhibition: Design, Synthesis, and Biological Evaluation of C-7-Substituted 1,3-Benzothiazole Derivatives.
Authors: Okaniwa, M. / Hirose, M. / Arita, T. / Yabuki, M. / Nakamura, A. / Takagi, T. / Kawamoto, T. / Uchiyama, N. / Sumita, A. / Tsutsumi, S. / Tottori, T. / Inui, Y. / Sang, B.C. / Yano, J. / ...Authors: Okaniwa, M. / Hirose, M. / Arita, T. / Yabuki, M. / Nakamura, A. / Takagi, T. / Kawamoto, T. / Uchiyama, N. / Sumita, A. / Tsutsumi, S. / Tottori, T. / Inui, Y. / Sang, B.C. / Yano, J. / Aertgeerts, K. / Yoshida, S. / Ishikawa, T.
History
DepositionMay 17, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 24, 2013Provider: repository / Type: Initial release
Revision 1.1Sep 4, 2013Group: Database references
Revision 1.2Nov 15, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.3Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)65,7564
Polymers64,6452
Non-polymers1,1112
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
A: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,8782
Polymers32,3221
Non-polymers5561
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
B: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,8782
Polymers32,3221
Non-polymers5561
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)110.829, 110.829, 144.579
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212

-
Components

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


Mass: 32322.379 Da / Num. of mol.: 2 / Fragment: UNP residues 445-726
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: BRAF, V-RAF MURINE SARCOMA VIRAL ONCOGENE HOMOLOG B1, P94
Plasmid: pFASTBAC / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P15056, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-1SW / N-{7-cyano-6-[4-fluoro-3-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-1,3-benzothiazol-2-yl}cyclopropanecarboxamide


Mass: 555.503 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H17F4N5O3S

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.43 Å3/Da / Density % sol: 64.18 %
Crystal growTemperature: 277 K / Method: sitting drop, vapor diffusion / pH: 8.3
Details: 7.8% PEG 8000, 0.8M LiCl, 100 mM Tris pH 8.3, sitting drop, vapor diffusion, temperature 277K

-
Data collection

DiffractionMean temperature: 95 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Mar 4, 2011
RadiationMonochromator: Single Si(220) crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.3→50 Å / Num. all: 14150 / Num. obs: 14150 / % possible obs: 100 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 5.5 % / Rmerge(I) obs: 0.263 / Χ2: 1.003 / Net I/σ(I): 3.1
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
3.3-3.365.60.8670211100
3.36-3.425.60.7726780.9631100
3.42-3.485.60.7296930.9991100
3.48-3.555.70.6436880.9661100
3.55-3.635.60.5846891.0031100
3.63-3.725.60.4226950.9931100
3.72-3.815.60.3886970.9551100
3.81-3.915.60.3346810.9931100
3.91-4.035.60.316941.0431100
4.03-4.165.50.2827001.0031100
4.16-4.315.60.2546950.9881100
4.31-4.485.50.2187111.0191100
4.48-4.685.50.2136901.0361100
4.68-4.935.50.2037111.0721100
4.93-5.245.40.2367081.0191100
5.24-5.645.30.2547121.061100
5.64-6.215.30.2897201.008199.9
6.21-7.15.20.197280.9881100
7.1-8.945.30.09174111100
8.94-504.90.0458170.9591100

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
REFMAC5.7.0029refinement
PDB_EXTRACT3.11data extraction
HKL-2000data collection
DENZOdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.3→40 Å / Cor.coef. Fo:Fc: 0.92 / Cor.coef. Fo:Fc free: 0.878 / Occupancy max: 1 / Occupancy min: 1 / SU B: 48.885 / SU ML: 0.354 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.481 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2562 720 5.1 %RANDOM
Rwork0.2057 ---
obs0.2083 14103 99.82 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 115.59 Å2 / Biso mean: 53.3118 Å2 / Biso min: 32.7 Å2
Baniso -1Baniso -2Baniso -3
1--1 Å2-0 Å2-0 Å2
2---1 Å2-0 Å2
3---1.99 Å2
Refinement stepCycle: LAST / Resolution: 3.3→40 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4093 0 78 0 4171
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.0194267
X-RAY DIFFRACTIONr_bond_other_d0.0010.024108
X-RAY DIFFRACTIONr_angle_refined_deg1.1321.9835771
X-RAY DIFFRACTIONr_angle_other_deg0.69239443
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.6275509
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.17123.859184
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.66315766
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.4351526
X-RAY DIFFRACTIONr_chiral_restr0.0590.2626
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0214755
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02965
LS refinement shellResolution: 3.302→3.387 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.314 50 -
Rwork0.277 963 -
all-1013 -
obs--99.61 %
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)
14.20730.78952.26812.88750.37537.3818-0.0722-0.6364-0.3420.225-0.1451-0.82780.15920.60460.21730.16120.04410.02390.25040.11090.316448.7258-31.014513.175
21.336-0.9511-1.68574.75221.04012.42770.09130.16210.0822-0.25550.0293-0.02-0.1986-0.0194-0.12060.1188-0.0253-0.00620.159-0.00730.042943.3556-43.3099-9.5136
32.2459-0.1543-0.45825.521-0.61124.50620.08450.32340.7758-0.5527-0.31560.0282-0.6865-0.32930.23110.30230.10070.01270.10290.06370.356135.8602-12.3685-2.8111
43.808-1.3974-0.97922.30521.62132.24820.10580.0485-0.05560.2169-0.09-0.09760.09620.0281-0.01580.0907-0.0150.03260.02590.00880.07120.797-15.781518.331
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A447 - 532
2X-RAY DIFFRACTION2A533 - 721
3X-RAY DIFFRACTION3B448 - 532
4X-RAY DIFFRACTION4B533 - 719
5X-RAY DIFFRACTION4B901

+
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