[English] 日本語
Yorodumi
- PDB-6scm: SOS1 in Complex with Inhibitor BI-3406 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6scm
TitleSOS1 in Complex with Inhibitor BI-3406
ComponentsSon of sevenless homolog 1
KeywordsONCOPROTEIN / Oncology / exchange factor / protein-ligand complex
Function / homology
Function and homology information


midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / Interleukin-15 signaling / Activation of RAC1 ...midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / Interleukin-15 signaling / Activation of RAC1 / positive regulation of small GTPase mediated signal transduction / Signaling by LTK / blood vessel morphogenesis / epidermal growth factor receptor binding / positive regulation of epidermal growth factor receptor signaling pathway / Regulation of KIT signaling / leukocyte migration / NRAGE signals death through JNK / eyelid development in camera-type eye / Fc-epsilon receptor signaling pathway / roof of mouth development / neurotrophin TRK receptor signaling pathway / GRB2:SOS provides linkage to MAPK signaling for Integrins / B cell homeostasis / regulation of T cell proliferation / RET signaling / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / hair follicle development / fibroblast growth factor receptor signaling pathway / Role of LAT2/NTAL/LAB on calcium mobilization / Signalling to RAS / Interleukin receptor SHC signaling / Signal attenuation / Activated NTRK2 signals through FRS2 and FRS3 / SHC-related events triggered by IGF1R / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Schwann cell development / SHC-mediated cascade:FGFR2 / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / Tie2 Signaling / FRS-mediated FGFR1 signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / RAC1 GTPase cycle / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / myelination / EGFR Transactivation by Gastrin / NCAM signaling for neurite out-growth / FCERI mediated Ca+2 mobilization / GRB2 events in ERBB2 signaling / Downstream signal transduction / SHC1 events in ERBB2 signaling / Insulin receptor signalling cascade / GTPase activator activity / insulin-like growth factor receptor signaling pathway / axon guidance / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Constitutive Signaling by Overexpressed ERBB2 / T cell activation / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / guanyl-nucleotide exchange factor activity / response to ischemia / B cell receptor signaling pathway / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / molecular condensate scaffold activity / Signaling by SCF-KIT / Constitutive Signaling by EGFRvIII / cytokine-mediated signaling pathway / Signaling by ERBB2 ECD mutants / multicellular organism growth / Signaling by ERBB2 KD Mutants / SH3 domain binding / epidermal growth factor receptor signaling pathway / Signaling by CSF1 (M-CSF) in myeloid cells / insulin receptor signaling pathway / DAP12 signaling / G alpha (12/13) signalling events / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / regulation of cell population proliferation / RAF/MAP kinase cascade / Potential therapeutics for SARS / Ras protein signal transduction
Similarity search - Function
Ras guanine-nucleotide exchange factor, conserved site / Ras Guanine-nucleotide exchange factors domain signature. / RasGEF N-terminal motif / Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif / Ras-like guanine nucleotide exchange factor, N-terminal / Ras-like guanine nucleotide exchange factor / Ras guanine-nucleotide exchange factors N-terminal domain profile. / Ras guanine nucleotide exchange factor domain superfamily / Ras guanine-nucleotide exchange factor, catalytic domain superfamily / RasGEF domain ...Ras guanine-nucleotide exchange factor, conserved site / Ras Guanine-nucleotide exchange factors domain signature. / RasGEF N-terminal motif / Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif / Ras-like guanine nucleotide exchange factor, N-terminal / Ras-like guanine nucleotide exchange factor / Ras guanine-nucleotide exchange factors N-terminal domain profile. / Ras guanine nucleotide exchange factor domain superfamily / Ras guanine-nucleotide exchange factor, catalytic domain superfamily / RasGEF domain / Ras guanine-nucleotide exchange factors catalytic domain profile. / Guanine nucleotide exchange factor for Ras-like small GTPases / Ras guanine-nucleotide exchange factors catalytic domain / : / SOS1/NGEF-like PH domain / Dbl homology (DH) domain superfamily / RhoGEF domain / Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases / Dbl homology (DH) domain / Dbl homology (DH) domain profile. / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / Histone-fold / PH-like domain superfamily
Similarity search - Domain/homology
IMIDAZOLE / Chem-L7H / Son of sevenless homolog 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.866 Å
AuthorsKessler, D. / Fischer, G. / Ramharter, J.
CitationJournal: Cancer Discov / Year: 2021
Title: BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition.
Authors: Hofmann, M.H. / Gmachl, M. / Ramharter, J. / Savarese, F. / Gerlach, D. / Marszalek, J.R. / Sanderson, M.P. / Kessler, D. / Trapani, F. / Arnhof, H. / Rumpel, K. / Botesteanu, D.A. / ...Authors: Hofmann, M.H. / Gmachl, M. / Ramharter, J. / Savarese, F. / Gerlach, D. / Marszalek, J.R. / Sanderson, M.P. / Kessler, D. / Trapani, F. / Arnhof, H. / Rumpel, K. / Botesteanu, D.A. / Ettmayer, P. / Gerstberger, T. / Kofink, C. / Wunberg, T. / Zoephel, A. / Fu, S.C. / Teh, J.L. / Bottcher, J. / Pototschnig, N. / Schachinger, F. / Schipany, K. / Lieb, S. / Vellano, C.P. / O'Connell, J.C. / Mendes, R.L. / Moll, J. / Petronczki, M. / Heffernan, T.P. / Pearson, M. / McConnell, D.B. / Kraut, N.
History
DepositionJul 24, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 26, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 10, 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.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jun 2, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year
Revision 1.3May 15, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Son of sevenless homolog 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)58,0149
Polymers57,1031
Non-polymers9118
Water6,846380
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1490 Å2
ΔGint25 kcal/mol
Surface area24360 Å2
MethodPISA
Unit cell
Length a, b, c (Å)38.007, 78.74, 168.924
Angle α, β, γ (deg.)90, 90, 90
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Son of sevenless homolog 1 / SOS-1


Mass: 57103.285 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SOS1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q07889
#2: Chemical ChemComp-IMD / IMIDAZOLE


Mass: 69.085 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H5N2
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-L7H / ~{N}-[(1~{R})-1-[3-azanyl-5-(trifluoromethyl)phenyl]ethyl]-7-methoxy-2-methyl-6-[(3~{S})-oxolan-3-yl]oxy-quinazolin-4-amine


Mass: 462.465 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C23H25F3N4O3 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 380 / 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: 2.21 Å3/Da / Density % sol: 44.43 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 13% PEG8000, 0.1M Imidazole pH=8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 4M / Detector: PIXEL / Date: Aug 8, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.866→84.462 Å / Num. obs: 34879 / % possible obs: 80.6 % / Redundancy: 9.6 % / CC1/2: 0.998 / Rmerge(I) obs: 0.132 / Rpim(I) all: 0.044 / Net I/σ(I): 12
Reflection shellResolution: 1.866→1.981 Å / Num. unique obs: 1744 / CC1/2: 0.342 / Rpim(I) all: 0.694

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
STARANISOdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.866→84.46 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.928 / SU R Cruickshank DPI: 0.65 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.217 / SU Rfree Blow DPI: 0.16 / SU Rfree Cruickshank DPI: 0.156
RfactorNum. reflection% reflectionSelection details
Rfree0.22 1717 -RANDOM
Rwork0.199 ---
obs0.2 34893 77.4 %-
Displacement parametersBiso mean: 32.1 Å2
Baniso -1Baniso -2Baniso -3
1--1.6611 Å20 Å20 Å2
2--0.9988 Å20 Å2
3---0.6624 Å2
Refine analyzeLuzzati coordinate error obs: 0.27 Å
Refinement stepCycle: LAST / Resolution: 1.866→84.46 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3875 0 63 380 4318
LS refinement shellResolution: 1.84→1.94 Å
RfactorNum. reflection% reflection
Rfree0.2177 42 -
Rwork0.2372 --
obs0.2361 698 11.06 %
Refinement TLS params.Origin x: 8.7326 Å / Origin y: -15.3206 Å / Origin z: -22.1583 Å
111213212223313233
T0 Å20 Å20 Å2-0 Å20 Å2--0 Å2
L0 °20 °20 °2-0 °20 °2--0 °2
S0 Å °0 Å °0 Å °0 Å °0 Å °0 Å °0 Å °0 Å °0 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