[English] 日本語
Yorodumi
- PDB-6cu6: Crystal structure of GMPPNP-bound G12R mutant of human KRAS4b -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cu6
TitleCrystal structure of GMPPNP-bound G12R mutant of human KRAS4b
ComponentsGTPase KRas
KeywordsONCOPROTEIN / KRAS / RAS / G12R / G12 / KRAS4b / K-RAS
Function / homology
Function and homology information


endocrine signaling / forebrain astrocyte development / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / epithelial tube branching involved in lung morphogenesis / type I pneumocyte differentiation / positive regulation of Rac protein signal transduction / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of glial cell proliferation ...endocrine signaling / forebrain astrocyte development / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / epithelial tube branching involved in lung morphogenesis / type I pneumocyte differentiation / positive regulation of Rac protein signal transduction / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of glial cell proliferation / Signaling by RAS GTPase mutants / Signaling by RAS GAP mutants / Activation of RAS in B cells / RUNX3 regulates p14-ARF / RAS signaling downstream of NF1 loss-of-function variants / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / Signalling to RAS / glial cell proliferation / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / homeostasis of number of cells within a tissue / Estrogen-stimulated signaling through PRKCZ / Signaling by PDGFRA extracellular domain mutants / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / SHC-mediated cascade:FGFR3 / Signaling by FGFR4 in disease / MET activates RAS signaling / SHC-mediated cascade:FGFR2 / Erythropoietin activates RAS / SHC-mediated cascade:FGFR4 / Signaling by FLT3 ITD and TKD mutants / SHC-mediated cascade:FGFR1 / Signaling by CSF3 (G-CSF) / FRS-mediated FGFR3 signaling / Tie2 Signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / FRS-mediated FGFR1 signaling / G protein activity / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / striated muscle cell differentiation / Ras activation upon Ca2+ influx through NMDA receptor / SHC1 events in EGFR signaling / p38MAPK events / Signaling by FLT3 fusion proteins / FLT3 Signaling / EGFR Transactivation by Gastrin / small monomeric GTPase / GRB2 events in ERBB2 signaling / Signaling by FGFR1 in disease / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / NCAM signaling for neurite out-growth / Insulin receptor signalling cascade / Constitutive Signaling by Overexpressed ERBB2 / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation / visual learning / regulation of long-term neuronal synaptic plasticity / RAF activation / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / Signaling by high-kinase activity BRAF mutants / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / MAP2K and MAPK activation / Ca2+ pathway / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / extrinsic component of cytoplasmic side of plasma membrane / Regulation of RAS by GAPs / GDP binding / regulation of protein stability / RAS processing / Negative regulation of MAPK pathway / actin cytoskeleton organization / Signaling by RAF1 mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / Signaling by moderate kinase activity BRAF mutants / Signaling by BRAF and RAF1 fusions / MAPK cascade / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / DAP12 signaling / Ras protein signal transduction / neuron apoptotic process / RAF/MAP kinase cascade / mitochondrial outer membrane / negative regulation of neuron apoptotic process / GTPase activity / positive regulation of protein phosphorylation / Golgi membrane / focal adhesion
Similarity search - Function
Small GTPase, Ras-type / small GTPase Ras family profile. / Rho (Ras homology) subfamily of Ras-like small GTPases / Small GTPase / Ras family / Small GTP-binding protein domain / P-loop containing nucleotide triphosphate hydrolases / P-loop containing nucleoside triphosphate hydrolase / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER / GTPase KRas
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsTran, T.H. / Simanshu, D.K.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)HHSN261200800001E United States
CitationJournal: Cancer Discov / Year: 2020
Title: Atypical KRASG12RMutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer.
Authors: Hobbs, G.A. / Baker, N.M. / Miermont, A.M. / Thurman, R.D. / Pierobon, M. / Tran, T.H. / Anderson, A.O. / Waters, A.M. / Diehl, J.N. / Papke, B. / Hodge, R.G. / Klomp, J.E. / Goodwin, C.M. / ...Authors: Hobbs, G.A. / Baker, N.M. / Miermont, A.M. / Thurman, R.D. / Pierobon, M. / Tran, T.H. / Anderson, A.O. / Waters, A.M. / Diehl, J.N. / Papke, B. / Hodge, R.G. / Klomp, J.E. / Goodwin, C.M. / DeLiberty, J.M. / Wang, J. / Ng, R.W.S. / Gautam, P. / Bryant, K.L. / Esposito, D. / Campbell, S.L. / Petricoin 3rd, E.F. / Simanshu, D.K. / Aguirre, A.J. / Wolpin, B.M. / Wennerberg, K. / Rudloff, U. / Cox, A.D. / Der, C.J.
History
DepositionMar 23, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 25, 2019Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2019Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Jan 22, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: GTPase KRas
B: GTPase KRas
C: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,01810
Polymers58,2873
Non-polymers1,7327
Water4,179232
1
A: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,9753
Polymers19,4291
Non-polymers5472
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,0684
Polymers19,4291
Non-polymers6393
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,9753
Polymers19,4291
Non-polymers5472
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)67.790, 83.295, 86.040
Angle α, β, γ (deg.)90.000, 110.100, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11B-583-

HOH

-
Components

#1: Protein GTPase KRas / K-Ras 2 / Ki-Ras / c-K-ras / c-Ki-ras


Mass: 19428.953 Da / Num. of mol.: 3 / Mutation: G12R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01116
#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GNP / PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER / 5'-Guanylyl imidodiphosphate


Mass: 522.196 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C10H17N6O13P3 / Feature type: SUBJECT OF INVESTIGATION
Comment: GppNHp, GMPPNP, energy-carrying molecule analogue*YM
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 232 / 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: 1.97 Å3/Da / Density % sol: 37.56 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 2.1 M Sodium Malonate pH 7.5, 40 mM Dimethyloctylphosphine oxide

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 3, 2017
Details: Cryogenically-cooled single crystal Si(220) side bounce monochromator
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 1.5→50.58 Å / Num. obs: 70088 / % possible obs: 95.5 % / Redundancy: 2.325 % / Biso Wilson estimate: 26.11 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.048 / Rrim(I) all: 0.061 / Χ2: 1.18 / Net I/σ(I): 8.93 / Num. measured all: 317030
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rrim(I) all% possible all
1.5-1.592.280.8730.91212550.51.12992
1.59-1.72.3120.5021.75204950.7640.64694.5
1.7-1.832.240.2773.35193520.9180.35895.8
1.83-2.012.4470.1556.68181110.9690.19797.5
2.01-2.242.3870.08711.3164640.9870.1197.6
2.24-2.592.2450.05715.09141940.9930.07396
2.59-3.172.3950.04419.85122070.9950.05797.1
3.17-4.472.3020.03923.0192640.9950.0595.5
4.47-50.582.340.03624.0550430.9950.04694.6

-
Processing

Software
NameVersionClassification
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: GMPPNP-bound KRAS4B

Resolution: 1.5→50.58 Å / SU ML: 0.21 / Cross valid method: THROUGHOUT / σ(F): 1.37 / Phase error: 29.1
RfactorNum. reflection% reflection
Rfree0.2296 1854 2.65 %
Rwork0.2024 --
obs0.2031 70088 97.64 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 115.27 Å2 / Biso mean: 40.7487 Å2 / Biso min: 18 Å2
Refinement stepCycle: final / Resolution: 1.5→50.58 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3847 0 105 232 4184
Biso mean--33.54 41.7 -
Num. residues----486
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 13

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.5-1.54060.371440.355089523394
1.5406-1.58590.34511350.31265101523696
1.5859-1.63710.32761380.28435107524596
1.6371-1.69560.32191390.27695183532297
1.6956-1.76350.30531450.26655233537898
1.7635-1.84380.27181390.24895268540798
1.8438-1.9410.31450.24425294543998
1.941-2.06260.23781500.22375310546099
2.0626-2.22180.21931410.21825311545299
2.2218-2.44540.26911430.21295309545299
2.4454-2.79930.22411400.21775295543599
2.7993-3.52660.20891470.195356550399
3.5266-50.6090.19691480.16455378552698

+
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