[English] 日本語
Yorodumi
- PDB-5us4: Crystal structure of human KRAS G12D mutant in complex with GDP -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5us4
TitleCrystal structure of human KRAS G12D mutant in complex with GDP
ComponentsGTPase KRas
KeywordsHYDROLASE / KRAS / GTPase
Function / homology
Function and homology information


forebrain astrocyte development / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / type I pneumocyte differentiation / epithelial tube branching involved in lung morphogenesis / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants ...forebrain astrocyte development / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / type I pneumocyte differentiation / epithelial tube branching involved in lung morphogenesis / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / 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 / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / Signalling to RAS / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / glial cell proliferation / Estrogen-stimulated signaling through PRKCZ / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / protein-membrane adaptor activity / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / positive regulation of glial cell proliferation / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / homeostasis of number of cells within a tissue / p38MAPK events / Tie2 Signaling / FRS-mediated FGFR1 signaling / Signaling by FGFR2 in disease / striated muscle cell differentiation / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / CD209 (DC-SIGN) signaling / Ras activation upon Ca2+ influx through NMDA receptor / NCAM signaling for neurite out-growth / SHC1 events in ERBB2 signaling / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / small monomeric GTPase / VEGFR2 mediated cell proliferation / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / RAF activation / Constitutive Signaling by EGFRvIII / regulation of long-term neuronal synaptic plasticity / Signaling by high-kinase activity BRAF mutants / Signaling by ERBB2 ECD mutants / MAP2K and MAPK activation / visual learning / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / G protein activity / cytoplasmic side of plasma membrane / Regulation of RAS by GAPs / Signaling by CSF1 (M-CSF) in myeloid cells / RAS processing / 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 / GDP binding / MAPK cascade / Signaling by BRAF and RAF1 fusions / DAP12 signaling / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / Ca2+ pathway / gene expression / actin cytoskeleton organization / RAF/MAP kinase cascade / neuron apoptotic process / negative regulation of neuron apoptotic process / Ras protein signal transduction / mitochondrial outer membrane / positive regulation of protein phosphorylation / Golgi membrane / focal adhesion
Similarity search - Function
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 / P-loop containing nucleotide triphosphate hydrolases ...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 / P-loop containing nucleotide triphosphate hydrolases / Rossmann fold / P-loop containing nucleoside triphosphate hydrolase / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
GUANOSINE-5'-DIPHOSPHATE / GTPase KRas
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.83 Å
AuthorsTran, T. / Kaplan, A. / Stockwell, B.R. / Tong, L.
CitationJournal: Cell / Year: 2017
Title: Multivalent Small-Molecule Pan-RAS Inhibitors.
Authors: Welsch, M.E. / Kaplan, A. / Chambers, J.M. / Stokes, M.E. / Bos, P.H. / Zask, A. / Zhang, Y. / Sanchez-Martin, M. / Badgley, M.A. / Huang, C.S. / Tran, T.H. / Akkiraju, H. / Brown, L.M. / ...Authors: Welsch, M.E. / Kaplan, A. / Chambers, J.M. / Stokes, M.E. / Bos, P.H. / Zask, A. / Zhang, Y. / Sanchez-Martin, M. / Badgley, M.A. / Huang, C.S. / Tran, T.H. / Akkiraju, H. / Brown, L.M. / Nandakumar, R. / Cremers, S. / Yang, W.S. / Tong, L. / Olive, K.P. / Ferrando, A. / Stockwell, B.R.
History
DepositionFeb 13, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 22, 2017Provider: repository / Type: Initial release
Revision 1.1Sep 27, 2017Group: Author supporting evidence / Category: pdbx_audit_support
Revision 1.2Mar 7, 2018Group: Data collection / Category: diffrn_source / Item: _diffrn_source.source
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 / pdbx_struct_conn_angle / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.value / _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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)44,1228
Polymers43,0022
Non-polymers1,1196
Water4,306239
1
A: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,0614
Polymers21,5011
Non-polymers5603
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,0614
Polymers21,5011
Non-polymers5603
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)93.822, 93.822, 121.352
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number146
Space group name H-MH3

-
Components

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


Mass: 21501.164 Da / Num. of mol.: 2 / Mutation: G12D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / References: UniProt: P01116
#2: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H15N5O11P2 / Comment: GDP, energy-carrying molecule*YM
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 239 / 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: 2.39 Å3/Da / Density % sol: 48.54 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 9.1
Details: 0.2 M sodium phosphate dibasic, 20% w/v PEG3350, pH 9.1

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-003 / Wavelength: 1.5418 Å
DetectorType: RIGAKU SATURN 944 / Detector: CCD / Date: Oct 7, 2015 / Details: MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.83→50 Å / Num. obs: 33643 / % possible obs: 95.7 % / Observed criterion σ(I): -3 / Redundancy: 2.8 % / Rmerge(I) obs: 0.048 / Net I/σ(I): 19.2
Reflection shellResolution: 1.83→1.9 Å / Redundancy: 2.4 % / Rmerge(I) obs: 0.239 / Mean I/σ(I) obs: 3.7 / % possible all: 97.2

-
Processing

Software
NameVersionClassification
DENZOdata reduction
SCALEPACKdata scaling
PHENIX1.9_1685refinement
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.83→38.525 Å / SU ML: 0.19 / Cross valid method: THROUGHOUT / σ(F): 1.97 / Phase error: 19.59
RfactorNum. reflection% reflection
Rfree0.2005 1687 5.02 %
Rwork0.164 --
obs0.1659 33635 95.61 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.83→38.525 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2611 0 70 241 2922
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.022719
X-RAY DIFFRACTIONf_angle_d1.7913673
X-RAY DIFFRACTIONf_dihedral_angle_d16.7141031
X-RAY DIFFRACTIONf_chiral_restr0.262418
X-RAY DIFFRACTIONf_plane_restr0.008464
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.8292-1.8830.2611410.21152682X-RAY DIFFRACTION96
1.883-1.94380.23641440.18462745X-RAY DIFFRACTION99
1.9438-2.01330.2621630.17322730X-RAY DIFFRACTION99
2.0133-2.09390.21661340.16852712X-RAY DIFFRACTION98
2.0939-2.18920.1941510.16212765X-RAY DIFFRACTION98
2.1892-2.30460.19621470.15392674X-RAY DIFFRACTION97
2.3046-2.44890.19141280.1662677X-RAY DIFFRACTION97
2.4489-2.6380.21721360.17312690X-RAY DIFFRACTION96
2.638-2.90340.20591290.18142666X-RAY DIFFRACTION95
2.9034-3.32330.18251450.16462611X-RAY DIFFRACTION94
3.3233-4.18620.19431340.14382547X-RAY DIFFRACTION92
4.1862-38.53310.17421350.15442449X-RAY DIFFRACTION88
Refinement TLS params.Method: refined / Origin x: -22.0053 Å / Origin y: 38.1037 Å / Origin z: -11.9575 Å
111213212223313233
T0.1092 Å20.0028 Å2-0.0162 Å2-0.1023 Å2-0.0106 Å2--0.1149 Å2
L1.1286 °20.3251 °2-0.3917 °2-0.7222 °2-0.2345 °2--0.6493 °2
S0.0043 Å °-0.0101 Å °-0.0178 Å °0.0028 Å °0.0056 Å °-0.0102 Å °0.0037 Å °0.0045 Å °-0.0145 Å °
Refinement TLS groupSelection details: all

+
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