[English] 日本語
Yorodumi
- PDB-6zj0: CRYSTAL STRUCTURE OF HRAS-G12D IN COMPLEX WITH GCP AND COMPOUND 18 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6zj0
TitleCRYSTAL STRUCTURE OF HRAS-G12D IN COMPLEX WITH GCP AND COMPOUND 18
ComponentsGTPase HRas
KeywordsHYDROLASE / GTPase
Function / homology
Function and homology information


phospholipase C activator activity / GTPase complex / oncogene-induced cell senescence / positive regulation of miRNA metabolic process / positive regulation of ruffle assembly / T-helper 1 type immune response / positive regulation of wound healing / defense response to protozoan / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / Signaling by RAS GAP mutants ...phospholipase C activator activity / GTPase complex / oncogene-induced cell senescence / positive regulation of miRNA metabolic process / positive regulation of ruffle assembly / T-helper 1 type immune response / positive regulation of wound healing / defense response to protozoan / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / 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 / positive regulation of protein targeting to membrane / SHC1 events in ERBB4 signaling / Signalling to RAS / adipose tissue development / Activated NTRK2 signals through FRS2 and FRS3 / SHC-related events triggered by IGF1R / Schwann cell development / Estrogen-stimulated signaling through PRKCZ / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR4 / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / Signaling by FGFR4 in disease / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / p38MAPK events / FRS-mediated FGFR1 signaling / Signaling by FGFR3 in disease / protein-membrane adaptor activity / Tie2 Signaling / Signaling by FGFR2 in disease / myelination / GRB2 events in EGFR signaling / EPHB-mediated forward signaling / SHC1 events in EGFR signaling / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / EGFR Transactivation by Gastrin / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / GRB2 events in ERBB2 signaling / Downstream signal transduction / intrinsic apoptotic signaling pathway / Insulin receptor signalling cascade / SHC1 events in ERBB2 signaling / Ras activation upon Ca2+ influx through NMDA receptor / Constitutive Signaling by Overexpressed ERBB2 / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / animal organ morphogenesis / VEGFR2 mediated cell proliferation / positive regulation of epithelial cell proliferation / small monomeric GTPase / regulation of actin cytoskeleton organization / positive regulation of JNK cascade / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / RAF activation / cellular response to gamma radiation / Signaling by SCF-KIT / Signaling by high-kinase activity BRAF mutants / Constitutive Signaling by EGFRvIII / regulation of long-term neuronal synaptic plasticity / MAP2K and MAPK activation / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / positive regulation of type II interferon production / endocytosis / positive regulation of fibroblast proliferation / chemotaxis / Regulation of RAS by GAPs / 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 / cellular senescence / Signaling by BRAF and RAF1 fusions / insulin receptor signaling pathway / DAP12 signaling / T cell receptor signaling pathway / MAPK cascade / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / regulation of cell population proliferation / G protein activity
Similarity search - Function
Small GTPase, Ras-type / Small GTPase Ras domain 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 nucleotide triphosphate hydrolases / Rossmann fold ...Small GTPase, Ras-type / Small GTPase Ras domain 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 nucleotide triphosphate hydrolases / Rossmann fold / P-loop containing nucleoside triphosphate hydrolase / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-EZZ / PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GTPase HRas
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.763 Å
AuthorsKessler, D. / Fischer, G. / Boettcher, J.
CitationJournal: Future Med Chem / Year: 2020
Title: Drugging all RAS isoforms with one pocket.
Authors: Kessler, D. / Bergner, A. / Bottcher, J. / Fischer, G. / Dobel, S. / Hinkel, M. / Mullauer, B. / Weiss-Puxbaum, A. / McConnell, D.B.
History
DepositionJun 26, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 19, 2020Provider: repository / Type: Initial release
Revision 1.1Nov 25, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 31, 2024Group: 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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,8815
Polymers18,9901
Non-polymers8914
Water3,099172
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1070 Å2
ΔGint-17 kcal/mol
Surface area7960 Å2
MethodPISA
Unit cell
Length a, b, c (Å)93.075, 93.075, 55.256
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number150
Space group name H-MP321
Components on special symmetry positions
IDModelComponents
11A-334-

HOH

21A-342-

HOH

31A-460-

HOH

41A-463-

HOH

-
Components

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


Mass: 18990.279 Da / Num. of mol.: 1
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
#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#3: Chemical ChemComp-GCP / PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER


Mass: 521.208 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H18N5O13P3 / Comment: GMP-PCP, energy-carrying molecule analogue*YM
#4: Chemical ChemComp-EZZ / (3~{S})-3-[2-[(dimethylamino)methyl]-1~{H}-indol-3-yl]-5-oxidanyl-2,3-dihydroisoindol-1-one


Mass: 321.373 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H19N3O2 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 172 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.64 Å3/Da / Density % sol: 66.19 %
Crystal growTemperature: 278 K / Method: vapor diffusion / Details: 30% PEG400, 200mM MgCl2, 100mM TRIS PH=8,5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Mar 7, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.763→80.61 Å / Num. obs: 22394 / % possible obs: 81.4 % / Redundancy: 14.9 % / Biso Wilson estimate: 38.08 Å2 / Rmerge(I) obs: 0.054 / Rsym value: 0.054 / Net I/σ(I): 27.9
Reflection shellResolution: 1.764→1.905 Å / Redundancy: 14.7 % / Mean I/σ(I) obs: 1.3 / Num. unique obs: 1119 / CC1/2: 0.524 / % possible all: 20

-
Processing

Software
NameVersionClassification
autoPROCdata reduction
XDS(VERSION Jan 26data reduction
autoPROC(Version 1.1.7)data scaling
STARANISOdata scaling
BUSTER2.11.7 (17-DEC-2019)refinement
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3L8Z

3l8z


Resolution: 1.763→80.61 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.945 / SU R Cruickshank DPI: 0.138 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.122 / SU Rfree Blow DPI: 0.117 / SU Rfree Cruickshank DPI: 0.112
RfactorNum. reflection% reflectionSelection details
Rfree0.2276 1119 5 %RANDOM
Rwork0.1984 ---
obs0.1999 22394 81.2 %-
Displacement parametersBiso mean: 52.4 Å2
Baniso -1Baniso -2Baniso -3
1--0.3162 Å20 Å20 Å2
2---0.3162 Å20 Å2
3---0.6325 Å2
Refine analyzeLuzzati coordinate error obs: 0.27 Å
Refinement stepCycle: LAST / Resolution: 1.763→80.61 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1290 0 58 172 1520
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0082673HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.934803HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d828SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes429HARMONIC5
X-RAY DIFFRACTIONt_it1371HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.55
X-RAY DIFFRACTIONt_other_torsion15.34
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion176SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies1HARMONIC1
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2263SEMIHARMONIC4
Refinement TLS params.Method: refined / Origin x: -27.3276 Å / Origin y: 34.3675 Å / Origin z: 11.967 Å
111213212223313233
T-0.1228 Å2-0.0503 Å20.0009 Å2-0.0035 Å2-0.0024 Å2---0.1322 Å2
L4.7398 °21.8776 °2-0.4512 °2-2.6089 °2-0.7027 °2--1.9008 °2
S0.1819 Å °-0.6404 Å °0.0675 Å °0.1612 Å °-0.182 Å °0.0678 Å °-0.088 Å °0.2711 Å °0.0001 Å °
Refinement TLS groupSelection details: { A|* }

+
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