[English] 日本語
Yorodumi
- PDB-7l0g: Monobody 12VC1 Bound to HRAS(G12C) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7l0g
TitleMonobody 12VC1 Bound to HRAS(G12C)
Components
  • GTPase HRas
  • Monobody 12VC1
KeywordsSIGNALING PROTEIN / RAS GTPase
Function / homology
Function and homology information


GTPase complex / oncogene-induced cell senescence / positive regulation of ruffle assembly / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / negative regulation of GTPase activity / T-helper 1 type immune response / positive regulation of wound healing / positive regulation of miRNA metabolic process / defense response to protozoan / Signaling by RAS GAP mutants ...GTPase complex / oncogene-induced cell senescence / positive regulation of ruffle assembly / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / negative regulation of GTPase activity / T-helper 1 type immune response / positive regulation of wound healing / positive regulation of miRNA metabolic process / defense response to protozoan / 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 / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / positive regulation of protein targeting to membrane / Signalling to RAS / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Estrogen-stimulated signaling through PRKCZ / adipose tissue development / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / : / Schwann cell development / 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 / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / protein-membrane adaptor activity / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / p38MAPK events / Tie2 Signaling / FRS-mediated FGFR1 signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EPHB-mediated forward signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / myelination / Ras activation upon Ca2+ influx through NMDA receptor / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / intrinsic apoptotic signaling pathway / small monomeric GTPase / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / G protein activity / positive regulation of GTPase activity / VEGFR2 mediated cell proliferation / positive regulation of epithelial cell proliferation / regulation of actin cytoskeleton organization / FCERI mediated MAPK activation / animal organ morphogenesis / positive regulation of JNK cascade / Signaling by ERBB2 TMD/JMD mutants / RAF activation / regulation of long-term neuronal synaptic plasticity / positive regulation of MAP kinase activity / Signaling by high-kinase activity BRAF mutants / Constitutive Signaling by EGFRvIII / MAP2K and MAPK activation / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / cellular response to gamma radiation / Regulation of RAS by GAPs / endocytosis / Negative regulation of MAPK pathway / RAS processing / 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 / chemotaxis / MAPK cascade / cellular senescence / Signaling by BRAF and RAF1 fusions / positive regulation of type II interferon production / positive regulation of fibroblast proliferation / insulin receptor signaling pathway / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
Similarity search - Function
Small GTPase, Ras-type / small GTPase Ras family profile. / 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 nucleoside triphosphate hydrolase
Similarity search - Domain/homology
5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE / GTPase HRas
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.54 Å
AuthorsTeng, K.W. / Hattori, T. / Tsai, S. / Koide, S.
Funding support United States, 4items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA194864 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA212608 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)F32 CA225131 United States
American Cancer SocietyPF-18-180-01-TBE United States
CitationJournal: Nat Commun / Year: 2021
Title: Selective and noncovalent targeting of RAS mutants for inhibition and degradation.
Authors: Teng, K.W. / Tsai, S.T. / Hattori, T. / Fedele, C. / Koide, A. / Yang, C. / Hou, X. / Zhang, Y. / Neel, B.G. / O'Bryan, J.P. / Koide, S.
History
DepositionDec 11, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 24, 2021Provider: repository / Type: Initial release
Revision 1.1May 26, 2021Group: 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.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: GTPase HRas
B: GTPase HRas
C: Monobody 12VC1
D: Monobody 12VC1
E: GTPase HRas
F: Monobody 12VC1
G: GTPase HRas
H: Monobody 12VC1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,20616
Polymers116,9528
Non-polymers2,2548
Water95553
1
A: GTPase HRas
C: Monobody 12VC1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,8014
Polymers29,2382
Non-polymers5642
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2920 Å2
ΔGint-29 kcal/mol
Surface area11950 Å2
MethodPISA
2
B: GTPase HRas
D: Monobody 12VC1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,8014
Polymers29,2382
Non-polymers5642
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2860 Å2
ΔGint-29 kcal/mol
Surface area11950 Å2
MethodPISA
3
E: GTPase HRas
F: Monobody 12VC1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,8014
Polymers29,2382
Non-polymers5642
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2850 Å2
ΔGint-28 kcal/mol
Surface area11800 Å2
MethodPISA
4
G: GTPase HRas
H: Monobody 12VC1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,8014
Polymers29,2382
Non-polymers5642
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2840 Å2
ΔGint-31 kcal/mol
Surface area11830 Å2
MethodPISA
Unit cell
Length a, b, c (Å)71.834, 62.596, 123.404
Angle α, β, γ (deg.)90.00, 101.22, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein
GTPase HRas / H-Ras-1 / Ha-Ras / Transforming protein p21 / c-H-ras / p21ras


Mass: 19008.359 Da / Num. of mol.: 4 / Mutation: G12C
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HRAS, HRAS1 / Production host: Escherichia coli (E. coli) / References: UniProt: P01112, small monomeric GTPase
#2: Antibody
Monobody 12VC1


Mass: 10229.587 Da / Num. of mol.: 4 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#3: Chemical
ChemComp-GSP / 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE


Mass: 539.246 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C10H16N5O13P3S
#4: Chemical
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Mg
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 53 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.37 Å3/Da / Density % sol: 48 % / Description: Clear, rod shape crystal
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.225 M Potassium sodium tartrate tetrahydrate, 15% w/v Polyethylene glycol 3,350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.979 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Mar 24, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 2.24→50 Å / Num. obs: 51349 / % possible obs: 98.6 % / Redundancy: 4.8 % / Rmerge(I) obs: 0.174 / Rpim(I) all: 0.091 / Rrim(I) all: 0.197 / Χ2: 0.896 / Net I/σ(I): 3.7 / Num. measured all: 247542
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.24-2.284.60.925190.7370.4621.0140.59799.1
2.28-2.324.70.83626160.7330.4240.9410.62299.6
2.32-2.364.80.81225350.7360.4090.9120.63699.3
2.36-2.414.80.69325880.8160.3480.7780.69398.9
2.41-2.474.70.65725020.7980.3370.7410.72598.2
2.47-2.524.50.58125460.8420.3020.6580.7697.8
2.52-2.595.20.5425750.8930.2640.6030.76799.9
2.59-2.665.10.45326020.9140.2210.5050.8899.8
2.66-2.735.10.41625720.910.2050.4650.89399.8
2.73-2.825.10.36125590.9270.1770.4031.03699.1
2.82-2.925.10.31425690.9380.1560.3521.23799.3
2.92-3.0450.2725760.9540.1340.3031.17199.4
3.04-3.184.80.22525720.9630.1140.2530.96898.6
3.18-3.354.60.19225330.9590.10.2171.02297.5
3.35-3.565.10.17525850.9730.0890.1971.0699.1
3.56-3.834.90.15526020.9760.0810.1761.04599.1
3.83-4.224.70.13725650.9790.0730.1560.98498.2
4.22-4.824.10.12224690.9760.0690.1410.90393.9
4.82-6.084.80.12125830.9820.0630.1370.91998.1
6.08-504.50.11826810.9880.0640.1340.90198.5

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4g0n

4g0n


Resolution: 2.54→46.84 Å / Cor.coef. Fo:Fc: 0.947 / Cor.coef. Fo:Fc free: 0.93 / SU B: 11.739 / SU ML: 0.246 / Cross valid method: THROUGHOUT / ESU R: 2.644 / ESU R Free: 0.296 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.22852 1780 5.1 %RANDOM
Rwork0.19456 ---
obs0.19633 33379 98.25 %-
Solvent computationIon probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.1 Å / Solvent model: MASK
Displacement parametersBiso mean: 53.323 Å2
Baniso -1Baniso -2Baniso -3
1--4.28 Å2-0 Å2-0.27 Å2
2--6.73 Å20 Å2
3----2.17 Å2
Refinement stepCycle: LAST / Resolution: 2.54→46.84 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8084 0 132 53 8269
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0198379
X-RAY DIFFRACTIONr_bond_other_d0.0010.027654
X-RAY DIFFRACTIONr_angle_refined_deg1.3441.88711419
X-RAY DIFFRACTIONr_angle_other_deg1.0662.92917756
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.98951026
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.8923.924367
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.6151382
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.9481552
X-RAY DIFFRACTIONr_chiral_restr0.090.21298
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.029236
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021688
X-RAY DIFFRACTIONr_mcbond_it3.2915.1784128
X-RAY DIFFRACTIONr_mcbond_other3.2915.1784127
X-RAY DIFFRACTIONr_mcangle_it5.0627.7565147
X-RAY DIFFRACTIONr_mcangle_other5.0617.7575147
X-RAY DIFFRACTIONr_scbond_it3.9675.6614251
X-RAY DIFFRACTIONr_scbond_other3.9685.6624249
X-RAY DIFFRACTIONr_scangle_other6.2628.2876274
X-RAY DIFFRACTIONr_long_range_B_refined8.90359.5838796
X-RAY DIFFRACTIONr_long_range_B_other8.90259.5868795
LS refinement shellResolution: 2.542→2.608 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.34 115 -
Rwork0.29 2300 -
obs--91.2 %

+
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://pdbjlvh1.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