[English] 日本語
Yorodumi
- PDB-7yce: KRas G12C in complex with Compound 7b -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7yce
TitleKRas G12C in complex with Compound 7b
ComponentsIsoform 2B of GTPase KRas
KeywordsONCOPROTEIN/inhibitor / ONCOPROTEIN-inhibitor complex
Function / homologysmall monomeric GTPase / Ca2+ pathway / GUANOSINE-5'-DIPHOSPHATE / Chem-IQN / Isoform 2B of GTPase KRas
Function and homology information
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsAmano, Y.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Bioorg.Med.Chem. / Year: 2022
Title: Discovery and biological evaluation of 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one derivatives as covalent inhibitors of KRAS G12C with favorable metabolic stability and anti-tumor activity.
Authors: Imaizumi, T. / Akaiwa, M. / Abe, T. / Nigawara, T. / Koike, T. / Satake, Y. / Watanabe, K. / Kaneko, O. / Amano, Y. / Mori, K. / Yamanaka, Y. / Nagashima, T. / Shimazaki, M. / Kuramoto, K.
History
DepositionJul 1, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 10, 2022Provider: repository / Type: Initial release
Revision 1.1Aug 17, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_last ..._citation.journal_volume / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform 2B of GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,5435
Polymers19,3591
Non-polymers1,1844
Water1,71195
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area880 Å2
ΔGint-19 kcal/mol
Surface area8280 Å2
MethodPISA
Unit cell
Length a, b, c (Å)94.809, 94.809, 119.410
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number155
Space group name H-MH32
Components on special symmetry positions
IDModelComponents
11A-392-

HOH

-
Components

-
Protein , 1 types, 1 molecules A

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


Mass: 19358.836 Da / Num. of mol.: 1 / Mutation: G12C, C118S
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, small monomeric GTPase

-
Non-polymers , 5 types, 99 molecules

#2: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 1 / 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.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-IQN / 1-[7-[6-chloranyl-2-(1-ethylpiperidin-4-yl)oxy-8-fluoranyl-7-(5-methyl-1~{H}-indazol-4-yl)quinazolin-4-yl]-2,7-diazaspiro[3.5]nonan-2-yl]propan-1-one


Mass: 620.160 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C33H39ClFN7O2 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 95 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.67 Å3/Da / Density % sol: 53.89 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 / Details: MES, ammonium sulfate, PEG550MME

-
Data collection

DiffractionMean temperature: 90 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.5418 Å
DetectorType: RIGAKU HyPix-6000HE / Detector: PIXEL / Date: Jun 9, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.8→22.94 Å / Num. obs: 17961 / % possible obs: 92.9 % / Redundancy: 8.7 % / CC1/2: 0.987 / Rmerge(I) obs: 0.068 / Rpim(I) all: 0.025 / Rrim(I) all: 0.073 / Net I/σ(I): 18.7
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.8-1.8410.30.1851194311630.9910.060.1955.3100
9-22.936.30.02210711700.9990.010.02439.594.4

-
Processing

Software
NameVersionClassification
Aimless0.7.4data scaling
REFMAC5.8.0257refinement
PDB_EXTRACT3.27data extraction
CrysalisProdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4L8G

4l8g


Resolution: 1.8→22.94 Å / Cor.coef. Fo:Fc: 0.88 / Cor.coef. Fo:Fc free: 0.872 / SU B: 4.501 / SU ML: 0.132 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.193 / ESU R Free: 0.164 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.291 933 5.2 %RANDOM
Rwork0.2737 ---
obs0.2747 16941 92.25 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 97.79 Å2 / Biso mean: 25.494 Å2 / Biso min: 8.49 Å2
Baniso -1Baniso -2Baniso -3
1--0.47 Å2-0.23 Å2-0 Å2
2---0.47 Å2-0 Å2
3---1.51 Å2
Refinement stepCycle: final / Resolution: 1.8→22.94 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1345 0 78 95 1518
Biso mean--24.37 29.56 -
Num. residues----169
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0121450
X-RAY DIFFRACTIONr_angle_refined_deg1.8081.7331969
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2495168
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.5822.69278
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.86215253
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.0661510
X-RAY DIFFRACTIONr_chiral_restr0.1230.2187
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.021144
LS refinement shellResolution: 1.8→1.847 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.279 75 -
Rwork0.224 1337 -
all-1412 -
obs--99.37 %

+
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