[English] 日本語
Yorodumi
- PDB-8qqg: Structure of BRAF in Complex With Exarafenib (KIN-2787). -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8qqg
TitleStructure of BRAF in Complex With Exarafenib (KIN-2787).
ComponentsSerine/threonine-protein kinase B-raf
KeywordsTRANSFERASE / Braf
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 / response to cAMP / positive regulation of stress fiber assembly / 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 / positive regulation of peptidyl-serine phosphorylation / T cell differentiation in thymus / cell body / 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 / protein kinase activity / neuron projection / 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 / 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
Similarity search - Domain/homology
Chem-WJ9 / Serine/threonine-protein kinase B-raf
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.979 Å
AuthorsSchmitt, A. / Costanzi, E. / Kania, R. / Chen, Y.K.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: Structure of BRAF in Complex With Exarafenib (KIN-2787).
Authors: Schmitt, A. / Costanzi, E. / Kania, R. / Chen, Y.K.
History
DepositionOct 4, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 24, 2024Provider: repository / Type: Initial release

-
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
C: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)95,86713
Polymers94,0543
Non-polymers1,81310
Water1,44180
1
A: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9795
Polymers31,3511
Non-polymers6284
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9444
Polymers31,3511
Non-polymers5923
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9444
Polymers31,3511
Non-polymers5923
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)206.778, 206.778, 149.382
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number98
Space group name H-MI4122
Components on special symmetry positions
IDModelComponents
11B-932-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
32A
42C
53B
63C

NCS domain segments:

Beg auth comp-ID: ASP / Beg label comp-ID: ASP / End auth comp-ID: LEU / End label comp-ID: LEU

Dom-IDComponent-IDEns-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
111AA448 - 7202 - 274
221BB448 - 7202 - 274
332AA448 - 7202 - 274
442CC448 - 7202 - 274
553BB447 - 7201 - 274
663CC447 - 7201 - 274

NCS ensembles :
IDDetails
1Local NCS retraints between domains: 1 2
2Local NCS retraints between domains: 3 4
3Local NCS retraints between domains: 5 6

-
Components

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


Mass: 31351.328 Da / Num. of mol.: 3
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-WJ9 / (3~{S})-~{N}-[4-methyl-3-[2-morpholin-4-yl-6-[[(2~{R})-1-oxidanylpropan-2-yl]amino]pyridin-4-yl]phenyl]-3-[2,2,2-tris(fluoranyl)ethyl]pyrrolidine-1-carboxamide


Mass: 521.575 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C26H34F3N5O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: Cl
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 80 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.39 Å3/Da / Density % sol: 71.97 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: 0.1 M Hepes pH 6.7, 3.9 M NaCl, 0.10 M SCN

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.999 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jul 13, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.999 Å / Relative weight: 1
ReflectionResolution: 2.979→146.214 Å / Num. obs: 29475 / % possible obs: 93.9 % / Redundancy: 15.9 % / CC1/2: 0.965 / Net I/σ(I): 6.9
Reflection shellResolution: 2.979→3.134 Å / Num. unique obs: 1472 / CC1/2: 0.359

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
XDSdata reduction
pointlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.979→146.214 Å / Cor.coef. Fo:Fc: 0.906 / Cor.coef. Fo:Fc free: 0.859 / SU B: 19.721 / SU ML: 0.336 / Cross valid method: FREE R-VALUE / ESU R: 1.005 / ESU R Free: 0.385
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2612 522 1.771 %
Rwork0.2239 28954 -
all0.225 --
obs-28954 88.586 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 56.222 Å2
Baniso -1Baniso -2Baniso -3
1--0.089 Å20 Å2-0 Å2
2---0.089 Å20 Å2
3---0.178 Å2
Refinement stepCycle: LAST / Resolution: 2.979→146.214 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6388 0 118 80 6586
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.0136517
X-RAY DIFFRACTIONr_bond_other_d0.0020.0176281
X-RAY DIFFRACTIONr_angle_refined_deg1.3491.668821
X-RAY DIFFRACTIONr_angle_other_deg1.0831.59714381
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7365791
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.66821.563320
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.57115.1441149
X-RAY DIFFRACTIONr_dihedral_angle_other_3_deg29.04206
X-RAY DIFFRACTIONr_dihedral_angle_4_deg12.9051541
X-RAY DIFFRACTIONr_dihedral_angle_6_deg11.9052012
X-RAY DIFFRACTIONr_dihedral_angle_other_6_deg11.286203
X-RAY DIFFRACTIONr_chiral_restr0.050.2849
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.027255
X-RAY DIFFRACTIONr_gen_planes_other0.0020.021516
X-RAY DIFFRACTIONr_nbd_refined0.1540.21012
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1480.25242
X-RAY DIFFRACTIONr_nbtor_refined0.1450.23071
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0710.22851
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1220.2101
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0060.21
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1740.217
X-RAY DIFFRACTIONr_nbd_other0.1570.294
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.0060.21
X-RAY DIFFRACTIONr_mcbond_it2.6086.2093185
X-RAY DIFFRACTIONr_mcbond_other2.6066.2083184
X-RAY DIFFRACTIONr_mcangle_it4.6559.2933969
X-RAY DIFFRACTIONr_mcangle_other4.6559.2943970
X-RAY DIFFRACTIONr_scbond_it1.9346.1313332
X-RAY DIFFRACTIONr_scbond_other1.9346.1313330
X-RAY DIFFRACTIONr_scangle_it3.599.1484852
X-RAY DIFFRACTIONr_scangle_other3.599.1484853
X-RAY DIFFRACTIONr_lrange_it6.93267.76823
X-RAY DIFFRACTIONr_lrange_other6.93267.7026821
X-RAY DIFFRACTIONr_ncsr_local_group_10.0450.052832
X-RAY DIFFRACTIONr_ncsr_local_group_20.0520.052908
X-RAY DIFFRACTIONr_ncsr_local_group_30.0330.052873
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)Weight position
11AX-RAY DIFFRACTIONLocal ncs0.044550.05
12BX-RAY DIFFRACTIONLocal ncs0.044550.05
23AX-RAY DIFFRACTIONLocal ncs0.051770.05
24CX-RAY DIFFRACTIONLocal ncs0.051770.05
35BX-RAY DIFFRACTIONLocal ncs0.033460.05
36CX-RAY DIFFRACTIONLocal ncs0.033460.05
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
2.979-3.0560.29940.3233100.32324090.8020.76513.03450.319
3.056-3.140.222200.29812600.29723760.7670.77853.87210.299
3.14-3.2310.363320.29718920.29823030.7370.78483.54320.296
3.231-3.3310.294450.28320500.28322410.7840.80693.48510.281
3.331-3.440.292350.27120800.27121560.8010.84798.09830.265
3.44-3.560.313400.25920410.2621020.8090.85799.00090.251
3.56-3.6950.289330.27519860.27520340.7970.84699.26250.263
3.695-3.8460.265450.25519060.25519520.8390.84199.94880.242
3.846-4.0160.373230.24718580.24818810.8330.8781000.229
4.016-4.2120.25310.20517670.20617980.9090.9271000.192
4.212-4.440.154250.18717010.18617260.9560.9481000.175
4.44-4.7090.303340.16815920.17116260.910.9561000.157
4.709-5.0340.162270.17115000.1715270.9490.9561000.158
5.034-5.4360.208310.18914110.1914420.9510.9471000.175
5.436-5.9550.195280.20712930.20713210.960.9411000.191
5.955-6.6560.325170.21411890.21612060.9130.9341000.195
6.656-7.6830.189200.21510550.21410750.9360.9381000.199
7.683-9.4030.302130.1759080.1779210.8820.9641000.178
9.403-13.2710.288110.1797210.187320.9590.9691000.188
13.271-146.2140.36480.3464340.3464460.8860.87299.10310.349

+
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