[English] 日本語
Yorodumi
- PDB-9bve: Identification of multiple ligand hotspots on SOS2, compound 9 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9bve
TitleIdentification of multiple ligand hotspots on SOS2, compound 9
ComponentsSon of sevenless homolog 2
KeywordsSIGNALING PROTEIN / small molecule complex crystal structure / SOS2 / guanosine nucleotide exchange factor / RAS-activator / oncogenes / inhibitor of SOS-mediated guanosine nucleotide exchange
Function / homology
Function and homology information


regulation of pro-B cell differentiation / regulation of T cell differentiation in thymus / Interleukin-15 signaling / positive regulation of small GTPase mediated signal transduction / Activation of RAC1 / NRAGE signals death through JNK / B cell homeostasis / regulation of T cell proliferation / RAC1 GTPase cycle / guanyl-nucleotide exchange factor activity ...regulation of pro-B cell differentiation / regulation of T cell differentiation in thymus / Interleukin-15 signaling / positive regulation of small GTPase mediated signal transduction / Activation of RAC1 / NRAGE signals death through JNK / B cell homeostasis / regulation of T cell proliferation / RAC1 GTPase cycle / guanyl-nucleotide exchange factor activity / G alpha (12/13) signalling events / insulin receptor signaling pathway / Ras protein signal transduction / protein heterodimerization activity / plasma membrane / cytosol
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
: / Son of sevenless homolog 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsPhan, J. / Fesik, S.W.
Funding support United States, 1items
OrganizationGrant numberCountry
Lustgarten Foundation United States
CitationJournal: J.Med.Chem. / Year: 2025
Title: Discovery of Small Molecules that Bind to Son of Sevenless 2 (SOS2).
Authors: Zak, K.M. / Waterson, A.G. / Geist, L. / Braun, N. / Hauer, K. / Rumpel, K. / Ramharter, J. / Stadtmueller, H. / Wolkerstorfer, B. / Schoenbauer, D. / Cui, J. / Phan, J. / Abbott, J.R. / ...Authors: Zak, K.M. / Waterson, A.G. / Geist, L. / Braun, N. / Hauer, K. / Rumpel, K. / Ramharter, J. / Stadtmueller, H. / Wolkerstorfer, B. / Schoenbauer, D. / Cui, J. / Phan, J. / Abbott, J.R. / Sarkar, D. / Hodges, T.R. / Arnold, A. / Sensintaffar, J.L. / Fesik, S.W. / Kessler, D.
History
DepositionMay 20, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 5, 2025Provider: repository / Type: Initial release
Revision 1.1Feb 26, 2025Group: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Son of sevenless homolog 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,8832
Polymers60,4921
Non-polymers3911
Water4,540252
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area25700 Å2
MethodPISA
Unit cell
Length a, b, c (Å)64.234, 86.349, 106.587
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Son of sevenless homolog 2 / SOS-2


Mass: 60492.211 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SOS2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q07890
#2: Chemical ChemComp-A1ASY / N-(1H-indol-5-yl)-4-[4-(propan-2-yl)piperazin-1-yl]-5,6,7,8-tetrahydroquinazolin-2-amine


Mass: 390.525 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H30N6 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 252 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.44 Å3/Da / Density % sol: 49.66 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 22% PEG3350, 100 mM Bis-Tris propane, pH 7.5, 200 mM sodium sulfate, 5% glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.978 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Aug 18, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.978 Å / Relative weight: 1
ReflectionResolution: 1.83→50 Å / Num. obs: 28277 / % possible obs: 100 % / Redundancy: 6.7 % / CC1/2: 0.99 / Rmerge(I) obs: 0.091 / Rpim(I) all: 0.038 / Rrim(I) all: 0.099 / Net I/σ(I): 15.8
Reflection shellResolution: 1.83→1.86 Å / Redundancy: 1.9 % / Num. unique obs: 2621 / CC1/2: 0.66

-
Processing

Software
NameVersionClassification
PHENIX(1.15.2_3472: ???)refinement
SAINTdata scaling
SAINTdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.4→17.939 Å / SU ML: 0.38 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 32.44 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.3053 1143 5.01 %
Rwork0.254 --
obs0.2565 22815 95.99 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.4→17.939 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3912 0 29 255 4196
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0044084
X-RAY DIFFRACTIONf_angle_d0.6085524
X-RAY DIFFRACTIONf_dihedral_angle_d17.1372535
X-RAY DIFFRACTIONf_chiral_restr0.04596
X-RAY DIFFRACTIONf_plane_restr0.004713
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.4-2.5090.37271290.32272449X-RAY DIFFRACTION89
2.509-2.64080.38661420.31872698X-RAY DIFFRACTION97
2.6408-2.80570.34731430.31122702X-RAY DIFFRACTION97
2.8057-3.02140.36411450.30722745X-RAY DIFFRACTION99
3.0214-3.32370.3451440.31042741X-RAY DIFFRACTION98
3.3237-3.80070.29781380.27782641X-RAY DIFFRACTION93
3.8007-4.77350.2761450.20542758X-RAY DIFFRACTION97
4.7735-17.9390.24041570.18132938X-RAY DIFFRACTION99
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.2120.12330.59151.16420.74861.3882-0.00130.0877-0.0275-0.3226-0.14280.1215-0.02220.05060.15920.26820.0315-0.04190.3901-0.03310.2811-17.6463-16.0572-27.5865
21.6490.53120.27362.31730.28642.55890.0794-0.08560.01360.0019-0.14870.14680.2757-0.26220.00670.24760.01330.02170.2124-0.02330.2081-21.8107-17.0962-15.6277
31.90330.16250.99120.36090.22250.22350.2615-0.3978-0.34470.6282-0.28520.1587-0.0072-0.1013-0.00620.5374-0.06230.03730.30870.02290.3341-8.3809-11.52820.253
43.18941.39850.2942.2622-0.20440.83970.0338-0.03510.06790.11210.0080.09770.0253-0.0446-0.03840.20610.00640.01340.1748-0.02040.187322.42438.3785-4.6854
52.42770.38970.33921.9067-0.38561.2590.00540.7258-0.0929-0.14480.10070.0630.49810.0067-0.05240.37620.01530.02360.3101-0.03030.254522.43280.1627-18.0965
62.7920.8321.22933.34311.23844.12490.2671.14420.5605-0.6408-0.1237-0.5789-0.05690.6372-0.33320.3894-0.04910.09010.43740.05890.3918-2.4681-3.0923-24.9248
71.3816-0.5322-0.19413.21820.17290.95220.15470.0391-0.39610.2068-0.16290.36540.1105-0.20180.03560.2725-0.0281-0.00850.3818-0.00410.292917.46624.8472.7865
81.9033-0.55150.57421.85950.06421.94590.0759-0.08740.44-0.0108-0.0809-0.4185-0.2764-0.04360.01830.3455-0.08570.06940.34510.05170.332433.119121.3517-5.1895
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid -4 through 622 )
2X-RAY DIFFRACTION2chain 'A' and (resid 623 through 701 )
3X-RAY DIFFRACTION3chain 'A' and (resid 702 through 762 )
4X-RAY DIFFRACTION4chain 'A' and (resid 763 through 896 )
5X-RAY DIFFRACTION5chain 'A' and (resid 897 through 945 )
6X-RAY DIFFRACTION6chain 'A' and (resid 946 through 976 )
7X-RAY DIFFRACTION7chain 'A' and (resid 977 through 1003 )
8X-RAY DIFFRACTION8chain 'A' and (resid 1004 through 1045 )

+
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