[English] 日本語
Yorodumi
- PDB-6ob3: Crystal structure of G13D-KRAS (GMPPNP-bound) in complex with GAP... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ob3
TitleCrystal structure of G13D-KRAS (GMPPNP-bound) in complex with GAP-related domain (GRD) of neurofibromin (NF1)
Components
  • GTPase KRas
  • Neurofibromin
KeywordsSIGNALING PROTEIN/GTP Binding / KRAS / RAS / KRAS4b / NF1 / GAP / Neurofibromin / G13D / SIGNALING PROTEIN-GTP Binding complex
Function / homology
Function and homology information


positive regulation of mast cell apoptotic process / negative regulation of Rac protein signal transduction / regulation of glial cell differentiation / gamma-aminobutyric acid secretion, neurotransmission / observational learning / Schwann cell migration / negative regulation of Schwann cell migration / vascular associated smooth muscle cell migration / amygdala development / mast cell apoptotic process ...positive regulation of mast cell apoptotic process / negative regulation of Rac protein signal transduction / regulation of glial cell differentiation / gamma-aminobutyric acid secretion, neurotransmission / observational learning / Schwann cell migration / negative regulation of Schwann cell migration / vascular associated smooth muscle cell migration / amygdala development / mast cell apoptotic process / negative regulation of mast cell proliferation / Schwann cell proliferation / vascular associated smooth muscle cell proliferation / mast cell proliferation / glutamate secretion, neurotransmission / negative regulation of Schwann cell proliferation / negative regulation of leukocyte migration / negative regulation of vascular associated smooth muscle cell migration / positive regulation of adenylate cyclase activity / regulation of cell-matrix adhesion / forebrain morphogenesis / negative regulation of neurotransmitter secretion / hair follicle maturation / regulation of blood vessel endothelial cell migration / cell communication / smooth muscle tissue development / camera-type eye morphogenesis / negative regulation of oligodendrocyte differentiation / sympathetic nervous system development / myelination in peripheral nervous system / myeloid leukocyte migration / phosphatidylcholine binding / phosphatidylethanolamine binding / peripheral nervous system development / metanephros development / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / collagen fibril organization / endothelial cell proliferation / regulation of bone resorption / regulation of long-term synaptic potentiation / neural tube development / regulation of postsynapse organization / forebrain astrocyte development / pigmentation / artery morphogenesis / negative regulation of neuroblast proliferation / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / epithelial tube branching involved in lung morphogenesis / adrenal gland development / negative regulation of protein import into nucleus / type I pneumocyte differentiation / negative regulation of cell-matrix adhesion / spinal cord development / regulation of GTPase activity / negative regulation of MAPK cascade / Rac protein signal transduction / oligodendrocyte differentiation / skeletal muscle cell differentiation / negative regulation of osteoclast differentiation / positive regulation of Rac protein signal transduction / negative regulation of endothelial cell proliferation / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / RAS signaling downstream of NF1 loss-of-function variants / RUNX3 regulates p14-ARF / negative regulation of astrocyte differentiation / neuroblast proliferation / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / extrinsic apoptotic signaling pathway via death domain receptors / SHC1 events in ERBB4 signaling / Signalling to RAS / glial cell proliferation / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / regulation of angiogenesis / Estrogen-stimulated signaling through PRKCZ / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Schwann cell development / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / negative regulation of stem cell proliferation / negative regulation of fibroblast proliferation / homeostasis of number of cells within a tissue / skeletal muscle tissue development / protein-membrane adaptor activity / positive regulation of glial cell proliferation / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants
Similarity search - Function
Ras GTPase-activating protein / Ras GTPase-activating protein, conserved site / Ras GTPase-activating proteins domain signature. / GTPase-activator protein for Ras-like GTPase / Ras GTPase-activating proteins profile. / GTPase-activator protein for Ras-like GTPases / Ras GTPase-activating domain / Divergent CRAL/TRIO domain / CRAL-TRIO lipid binding domain profile. / Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) ...Ras GTPase-activating protein / Ras GTPase-activating protein, conserved site / Ras GTPase-activating proteins domain signature. / GTPase-activator protein for Ras-like GTPase / Ras GTPase-activating proteins profile. / GTPase-activator protein for Ras-like GTPases / Ras GTPase-activating domain / Divergent CRAL/TRIO domain / CRAL-TRIO lipid binding domain profile. / Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) / CRAL-TRIO lipid binding domain / CRAL-TRIO lipid binding domain superfamily / Rho GTPase activation protein / Small GTPase, Ras-type / small GTPase Ras family profile. / Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Small GTP-binding protein domain / PH-like domain superfamily / Armadillo-type fold / 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 / Neurofibromin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.1 Å
AuthorsTran, T.H. / Dharmaiah, S. / Simanshu, D.K.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2019
Title: KRAS G13D sensitivity to neurofibromin-mediated GTP hydrolysis.
Authors: Rabara, D. / Tran, T.H. / Dharmaiah, S. / Stephens, R.M. / McCormick, F. / Simanshu, D.K. / Holderfield, M.
History
DepositionMar 19, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 16, 2019Provider: repository / Type: Initial release
Revision 1.1Oct 30, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Nov 13, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)99,43316
Polymers97,2574
Non-polymers2,17612
Water5,639313
1
A: GTPase KRas
B: Neurofibromin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,8329
Polymers48,6292
Non-polymers1,2037
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: GTPase KRas
D: Neurofibromin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,6017
Polymers48,6292
Non-polymers9725
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)81.677, 97.169, 155.525
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and (resid 1 through 30 or (resid 31...
21(chain C and (resid 1 through 93 or resid 95 through 117 or resid 119 through 166))
12(chain B and (resid 1219 through 1268 or (resid 1269...
22(chain D and (resid 1219 through 1285 or resid 1287...

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
111METMETASPASP(chain A and (resid 1 through 30 or (resid 31...AA1 - 302 - 31
121GLUGLUGLUGLU(chain A and (resid 1 through 30 or (resid 31...AA3132
131GLYGLYLYSLYS(chain A and (resid 1 through 30 or (resid 31...AA0 - 1691 - 170
141GLYGLYLYSLYS(chain A and (resid 1 through 30 or (resid 31...AA0 - 1691 - 170
151GLYGLYLYSLYS(chain A and (resid 1 through 30 or (resid 31...AA0 - 1691 - 170
161GLYGLYLYSLYS(chain A and (resid 1 through 30 or (resid 31...AA0 - 1691 - 170
211METMETILEILE(chain C and (resid 1 through 93 or resid 95 through 117 or resid 119 through 166))CC1 - 932 - 94
221HISHISLYSLYS(chain C and (resid 1 through 93 or resid 95 through 117 or resid 119 through 166))CC95 - 11796 - 118
231ASPASPHISHIS(chain C and (resid 1 through 93 or resid 95 through 117 or resid 119 through 166))CC119 - 166120 - 167
112GLYGLYALAALA(chain B and (resid 1219 through 1268 or (resid 1269...BB1219 - 126812 - 61
122ASPASPASPASP(chain B and (resid 1219 through 1268 or (resid 1269...BB126962
132GLYGLYSERSER(chain B and (resid 1219 through 1268 or (resid 1269...BB1219 - 146312 - 256
142GLYGLYSERSER(chain B and (resid 1219 through 1268 or (resid 1269...BB1219 - 146312 - 256
152GLYGLYSERSER(chain B and (resid 1219 through 1268 or (resid 1269...BB1219 - 146312 - 256
162GLYGLYSERSER(chain B and (resid 1219 through 1268 or (resid 1269...BB1219 - 146312 - 256
212GLYGLYMETMET(chain D and (resid 1219 through 1285 or resid 1287...DD1219 - 128512 - 78
222PHEPHESERSER(chain D and (resid 1219 through 1285 or resid 1287...DD1287 - 131280 - 105
232ASPASPVALVAL(chain D and (resid 1219 through 1285 or resid 1287...DD1313 - 1317106 - 110
242ASPASPSERSER(chain D and (resid 1219 through 1285 or resid 1287...DD1217 - 146310 - 256
252ASPASPSERSER(chain D and (resid 1219 through 1285 or resid 1287...DD1217 - 146310 - 256
262ASPASPSERSER(chain D and (resid 1219 through 1285 or resid 1287...DD1217 - 146310 - 256
272ASPASPSERSER(chain D and (resid 1219 through 1285 or resid 1287...DD1217 - 146310 - 256

NCS ensembles :
ID
1
2

-
Components

-
Protein , 2 types, 4 molecules ACBD

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


Mass: 19386.848 Da / Num. of mol.: 2 / Mutation: G13D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P01116
#2: Protein Neurofibromin / / Neurofibromatosis-related protein NF-1


Mass: 29241.848 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NF1 / Production host: unidentified baculovirus / References: UniProt: P21359

-
Non-polymers , 5 types, 325 molecules

#3: Chemical ChemComp-GNP / PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER / 5'-Guanylyl imidodiphosphate


Mass: 522.196 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H17N6O13P3 / Feature type: SUBJECT OF INVESTIGATION
Comment: GppNHp, GMPPNP, energy-carrying molecule analogue*YM
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Cl
#6: Chemical
ChemComp-MES / 2-(N-MORPHOLINO)-ETHANESULFONIC ACID / MES (buffer)


Mass: 195.237 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C6H13NO4S / Comment: pH buffer*YM
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 313 / 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: 3.23 Å3/Da / Density % sol: 61.97 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6
Details: 0.1 M MES pH 6.0 and 25% Pentaerythritol propoxylate (5/4 PO/OH)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 10, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 2.1→97.169 Å / Num. obs: 72838 / % possible obs: 99.6 % / Redundancy: 4.811 % / Biso Wilson estimate: 49.658 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.052 / Rrim(I) all: 0.059 / Χ2: 1.158 / Net I/σ(I): 17.26 / Num. measured all: 350416
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rrim(I) all% possible all
2.1-2.234.8850.6792.68115520.8910.76298.9
2.23-2.384.6010.3994.19109590.9510.45199.7
2.38-2.575.0940.2696.42102550.9780.3100
2.57-2.814.9660.1649.7394430.990.18399.9
2.81-3.154.8670.09115.8885910.9960.10299.9
3.15-3.634.5570.04727.0875560.9980.05399.4
3.63-4.454.8780.03142.4864860.9990.03499.9
4.45-6.284.6460.02647.5650690.9990.02999.5
6.28-97.1694.4390.01956.23292710.02199.2

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6OB2

6ob2


Resolution: 2.1→77.763 Å / SU ML: 0.26 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 28.18
Details: Based on various parameters, the authors decided to cut-off the resolution to 2.10 Ang, and that value was used for calculating data collection statistics and for the structure refinement
RfactorNum. reflection% reflection
Rfree0.2259 1779 2.45 %
Rwork0.186 --
obs0.1869 72678 99.65 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 133.75 Å2 / Biso mean: 57.5982 Å2 / Biso min: 29.86 Å2
Refinement stepCycle: final / Resolution: 2.1→77.763 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6576 0 129 313 7018
Biso mean--69.45 60.23 -
Num. residues----828
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A1499X-RAY DIFFRACTION12.411TORSIONAL
12C1499X-RAY DIFFRACTION12.411TORSIONAL
21B2149X-RAY DIFFRACTION12.411TORSIONAL
22D2149X-RAY DIFFRACTION12.411TORSIONAL
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 (%)
2.1-2.15680.39261360.322554145550100
2.1568-2.22030.33691330.296653565489100
2.2203-2.29190.341350.275338547399
2.2919-2.37390.32091350.247753865521100
2.3739-2.46890.27751360.227954305566100
2.4689-2.58130.26731370.213754025539100
2.5813-2.71740.28511360.211154505586100
2.7174-2.88760.27981370.214854455582100
2.8876-3.11060.2541370.214454445581100
3.1106-3.42360.21331360.19315438557499
3.4236-3.9190.2241380.17155145652100
3.919-4.93740.17671390.139655415680100
4.9374-77.81580.17221440.15555741588599
Refinement TLS params.Method: refined / Origin x: 16.8414 Å / Origin y: -12.7081 Å / Origin z: -19.4087 Å
111213212223313233
T0.2786 Å20.0204 Å2-0.0032 Å2-0.5463 Å20.0102 Å2--0.2802 Å2
L0.3915 °20.295 °2-0.1613 °2-0.7205 °2-0.2577 °2--0.3438 °2
S-0.0306 Å °0.1179 Å °0.0002 Å °-0.0472 Å °-0.0163 Å °-0.1056 Å °-0.0219 Å °0.0125 Å °0.0529 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA0 - 169
2X-RAY DIFFRACTION1allB1219 - 1463
3X-RAY DIFFRACTION1allC1 - 166
4X-RAY DIFFRACTION1allD1217 - 1463
5X-RAY DIFFRACTION1allW1 - 328
6X-RAY DIFFRACTION1allL1 - 12

+
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