[English] 日本語
Yorodumi
- PDB-5hie: BRAF Kinase domain b3aC loop deletion mutant in complex with dabr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5hie
TitleBRAF Kinase domain b3aC loop deletion mutant in complex with dabrafenib
ComponentsSerine/threonine-protein kinase B-raf
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


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 / Signalling to p38 via RIT and RIN / head morphogenesis / endothelial cell apoptotic process / ARMS-mediated activation / negative regulation of fibroblast migration ...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 / Signalling to p38 via RIT and RIN / head morphogenesis / endothelial cell apoptotic process / ARMS-mediated activation / negative regulation of fibroblast migration / 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 / somatic stem cell population maintenance / regulation of T cell differentiation / face development / thyroid gland development / Negative feedback regulation of MAPK pathway / Frs2-mediated activation / stress fiber assembly / MAP kinase kinase activity / 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 / thymus development / postsynaptic modulation of chemical synaptic transmission / positive regulation of stress fiber assembly / substrate adhesion-dependent cell spreading / positive regulation of substrate adhesion-dependent cell spreading / T cell differentiation in thymus / animal organ morphogenesis / cellular response to calcium ion / sperm principal piece / sperm end piece / cellular response to xenobiotic stimulus / visual learning / RAF activation / Signaling by high-kinase activity BRAF mutants / Spry regulation of FGF signaling / MAP2K and MAPK activation / long-term synaptic potentiation / epidermal growth factor receptor signaling pathway / 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 / regulation of cell population proliferation / T cell receptor signaling pathway / presynapse / cell body / scaffold protein binding / cilium / negative regulation of neuron apoptotic process / positive regulation of ERK1 and ERK2 cascade / ciliary basal body / protein phosphorylation / protein kinase activity / non-specific serine/threonine protein kinase / postsynapse / neuron projection / protein serine kinase activity / protein serine/threonine kinase activity / positive regulation of gene expression / calcium ion binding / negative regulation of apoptotic process / glutamatergic synapse / mitochondrion / zinc ion binding / ATP binding / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm
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 / 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. / 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
Dabrafenib / Serine/threonine-protein kinase B-raf
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 3 Å
AuthorsWhalen, D.M. / Foster, S.A. / Ozen, A. / Wongchenko, M. / Yin, J. / Schaefer, G. / Mayfield, J. / Chmielecki, J. / Stephens, P. / Albacker, L. ...Whalen, D.M. / Foster, S.A. / Ozen, A. / Wongchenko, M. / Yin, J. / Schaefer, G. / Mayfield, J. / Chmielecki, J. / Stephens, P. / Albacker, L. / Yan, Y. / Song, K. / Hatzivassiliou, G. / Eigenbrot, C. / Yu, C. / Shaw, A.S. / Manning, G. / Skelton, N.J. / Hymowitz, S.G. / Malek, S.
CitationJournal: Cancer Cell / Year: 2016
Title: Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2.
Authors: Foster, S.A. / Whalen, D.M. / Ozen, A. / Wongchenko, M.J. / Yin, J. / Yen, I. / Schaefer, G. / Mayfield, J.D. / Chmielecki, J. / Stephens, P.J. / Albacker, L.A. / Yan, Y. / Song, K. / ...Authors: Foster, S.A. / Whalen, D.M. / Ozen, A. / Wongchenko, M.J. / Yin, J. / Yen, I. / Schaefer, G. / Mayfield, J.D. / Chmielecki, J. / Stephens, P.J. / Albacker, L.A. / Yan, Y. / Song, K. / Hatzivassiliou, G. / Eigenbrot, C. / Yu, C. / Shaw, A.S. / Manning, G. / Skelton, N.J. / Hymowitz, S.G. / Malek, S.
History
DepositionJan 11, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 6, 2016Provider: repository / Type: Initial release
Revision 1.1Apr 20, 2016Group: Database references
Revision 1.2Aug 3, 2016Group: Structure summary
Revision 1.3Mar 6, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength / pdbx_struct_oper_list
Item: _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
C: Serine/threonine-protein kinase B-raf
D: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)141,0198
Polymers138,9404
Non-polymers2,0784
Water88349
1
A: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,2552
Polymers34,7351
Non-polymers5201
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,2552
Polymers34,7351
Non-polymers5201
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,2552
Polymers34,7351
Non-polymers5201
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,2552
Polymers34,7351
Non-polymers5201
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)65.413, 127.786, 83.135
Angle α, β, γ (deg.)90.00, 105.79, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 34735.105 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P15056, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-P06 / Dabrafenib / N-{3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide


Mass: 519.562 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C23H20F3N5O2S2 / Comment: medication, anticancer, inhibitor*YM
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 49 / 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: 2.41 Å3/Da / Density % sol: 48.88 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 8.5 / Details: 0.1M Tris pH8.5, 19.3% PEG 8K, 500 mM NaCl

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Date: May 22, 2015
RadiationMonochromator: Liquid nitrogen-cooled double crystal, non fixed exit slit. Si(111)
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 3→35.28 Å / Num. obs: 25932 / % possible obs: 97.5 % / Redundancy: 3.45 % / Biso Wilson estimate: 73.94 Å2 / Rsym value: 0.125 / Net I/σ(I): 11.83
Reflection shellResolution: 3→3.12 Å / Redundancy: 3.45 % / Mean I/σ(I) obs: 2.58 / % possible all: 95.8

-
Processing

Software
NameVersionClassification
BUSTER2.11.5refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementResolution: 3→35.28 Å / Cor.coef. Fo:Fc: 0.9157 / Cor.coef. Fo:Fc free: 0.8846 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.364
RfactorNum. reflection% reflectionSelection details
Rfree0.221 1304 5.05 %RANDOM
Rwork0.1943 ---
obs0.1957 25832 97.96 %-
Displacement parametersBiso mean: 57.2 Å2
Baniso -1Baniso -2Baniso -3
1-7.3914 Å20 Å2-6.3594 Å2
2--1.0438 Å20 Å2
3----8.4352 Å2
Refine analyzeLuzzati coordinate error obs: 0.418 Å
Refinement stepCycle: LAST / Resolution: 3→35.28 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8211 0 140 49 8400
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0088541HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.0611544HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d3032SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes188HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1214HARMONIC5
X-RAY DIFFRACTIONt_it8541HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.36
X-RAY DIFFRACTIONt_other_torsion19.72
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1083SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact9872SEMIHARMONIC4
LS refinement shellResolution: 3→3.12 Å / Total num. of bins used: 13
RfactorNum. reflection% reflection
Rfree0.3119 130 4.44 %
Rwork0.2485 2798 -
all0.2514 2928 -
obs--97.96 %
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)
12.0483-0.6892-0.43533.86140.37540.8205-0.15610.1979-0.1548-0.06370.0233-0.21740.1723-0.19180.1328-0.1721-0.0312-0.0137-0.0618-0.02150.0433-45.041-2.398471.6963
25.2717-0.8459-0.40311.48450.61411.1164-0.10050.09750.3458-0.06390.0207-0.0663-0.1434-0.0370.0798-0.08830.0113-0.0787-0.1235-0.0155-0.0187-54.188814.898375.4272
33.3075-0.59660.43253.4637-1.00991.4491-0.06660.270.1925-0.07520.05250.0858-0.11060.11790.0141-0.1257-0.03140.0078-0.0934-0.0559-0.0276-87.94265.029171.3792
44.2803-1.20421.15211.8834-0.30860.6211-0.01870.0096-0.2772-0.0803-0.0894-0.02050.09510.08480.1081-0.13260.00770.0431-0.1309-0.01750.0647-78.8713-11.84676.4014
50.5746-0.86321.12496.4188-3.14894.3981-0.0679-0.10690.04710.02780.3034-0.03540.63890.2834-0.23560.07820.1633-0.0439-0.0291-0.1098-0.3594-49.7816-31.8579109.6629
62.5901-0.5071.29143.3649-2.81289.50360.2129-0.05390.12930.44010.30260.1444-0.37150.4677-0.5154-0.1603-0.0350.0474-0.2084-0.0922-0.0904-55.218-14.065102.0316
72.4705-0.8969-1.28524.9856-0.51242.3260.1217-0.09530.37910.49440.23330.2518-0.1152-0.046-0.355-0.0024-0.02310.012-0.1429-0.0375-0.1632-84.131437.0087106.7365
82.6369-0.1965-1.64233.51631.97476.2972-0.02850.0963-0.32770.4899-0.07960.08160.3691-0.07780.1081-0.0514-0.0053-0.029-0.20490.0024-0.1267-78.233818.895100.3648
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|454 - A|560 }
2X-RAY DIFFRACTION2{ A|561 - A|721 }
3X-RAY DIFFRACTION3{ B|454 - B|560 }
4X-RAY DIFFRACTION4{ B|561 - B|722 }
5X-RAY DIFFRACTION5{ C|454 - C|560 }
6X-RAY DIFFRACTION6{ C|561 - C|722 }
7X-RAY DIFFRACTION7{ D|454 - D|560 }
8X-RAY DIFFRACTION8{ D|561 - D|722 }

+
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