[English] 日本語
Yorodumi
- PDB-9fsh: Crystal structure of the HECT domain of Smurf 2 in complex with i... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9fsh
TitleCrystal structure of the HECT domain of Smurf 2 in complex with inhibitor 8
ComponentsE3 ubiquitin-protein ligase SMURF2
KeywordsLIGASE / E3 ubiquitin-protein ligase SMURF2 / HECT domain / inhibitor / allosteric inhibition / BMP signaling / pulmonary vascular remodeling
Function / homology
Function and homology information


regulation of transforming growth factor beta receptor signaling pathway / positive regulation of trophoblast cell migration / Signaling by BMP / HECT-type E3 ubiquitin transferase / Wnt signaling pathway, planar cell polarity pathway / SMAD binding / negative regulation of BMP signaling pathway / ubiquitin ligase complex / Downregulation of TGF-beta receptor signaling / Asymmetric localization of PCP proteins ...regulation of transforming growth factor beta receptor signaling pathway / positive regulation of trophoblast cell migration / Signaling by BMP / HECT-type E3 ubiquitin transferase / Wnt signaling pathway, planar cell polarity pathway / SMAD binding / negative regulation of BMP signaling pathway / ubiquitin ligase complex / Downregulation of TGF-beta receptor signaling / Asymmetric localization of PCP proteins / Degradation of AXIN / negative regulation of transforming growth factor beta receptor signaling pathway / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Regulation of RUNX3 expression and activity / Hedgehog 'on' state / ubiquitin-protein transferase activity / ubiquitin protein ligase activity / positive regulation of canonical Wnt signaling pathway / Antigen processing: Ubiquitination & Proteasome degradation / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / Ub-specific processing proteases / nuclear speck / protein ubiquitination / membrane raft / negative regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
E3 ubiquitin-protein ligase, SMURF1 type / : / HECT domain / HECT, E3 ligase catalytic domain / HECT-domain (ubiquitin-transferase) / HECT domain profile. / Domain Homologous to E6-AP Carboxyl Terminus with / Protein kinase C conserved region 2 (CalB) / C2 domain / WW domain ...E3 ubiquitin-protein ligase, SMURF1 type / : / HECT domain / HECT, E3 ligase catalytic domain / HECT-domain (ubiquitin-transferase) / HECT domain profile. / Domain Homologous to E6-AP Carboxyl Terminus with / Protein kinase C conserved region 2 (CalB) / C2 domain / WW domain / WW/rsp5/WWP domain signature. / C2 domain / C2 domain profile. / WW domain superfamily / WW/rsp5/WWP domain profile. / Domain with 2 conserved Trp (W) residues / WW domain / C2 domain superfamily
Similarity search - Domain/homology
PHOSPHATE ION / : / E3 ubiquitin-protein ligase SMURF2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.08 Å
AuthorsOstermann, N.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell / Year: 2025
Title: Therapeutic potential of allosteric HECT E3 ligase inhibition.
Authors: Rothman, A.M.K. / Florentin, A. / Zink, F. / Quigley, C. / Bonneau, O. / Hemmig, R. / Hachey, A. / Rejtar, T. / Thaker, M. / Jain, R. / Huang, S.M. / Sutton, D. / Roger, J. / Zhang, J.H. / ...Authors: Rothman, A.M.K. / Florentin, A. / Zink, F. / Quigley, C. / Bonneau, O. / Hemmig, R. / Hachey, A. / Rejtar, T. / Thaker, M. / Jain, R. / Huang, S.M. / Sutton, D. / Roger, J. / Zhang, J.H. / Weiler, S. / Cotesta, S. / Ottl, J. / Srivastava, S. / Kordonsky, A. / Avishid, R. / Yariv, E. / Rathi, R. / Khvalevsky, O. / Troxler, T. / Binmahfooz, S.K. / Kleifeld, O. / Morrell, N.W. / Humbert, M. / Thomas, M.J. / Jarai, G. / Beckwith, R.E.J. / Cobb, J.S. / Smith, N. / Ostermann, N. / Tallarico, J. / Shaw, D. / Guth-Gundel, S. / Prag, G. / Rowlands, D.J.
History
DepositionJun 21, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 16, 2025Provider: repository / Type: Initial release
Revision 1.1May 28, 2025Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase SMURF2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)58,6713
Polymers58,2041
Non-polymers4672
Water3,909217
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area150 Å2
ΔGint-4 kcal/mol
Surface area20040 Å2
Unit cell
Length a, b, c (Å)52.531, 71.75, 152.624
Angle α, β, γ (deg.)90, 90, 90
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein E3 ubiquitin-protein ligase SMURF2 / hSMURF2 / HECT-type E3 ubiquitin transferase SMURF2 / SMAD ubiquitination regulatory factor 2 / ...hSMURF2 / HECT-type E3 ubiquitin transferase SMURF2 / SMAD ubiquitination regulatory factor 2 / SMAD-specific E3 ubiquitin-protein ligase 2


Mass: 58203.914 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SMURF2 / Production host: Escherichia coli (E. coli)
References: UniProt: Q9HAU4, HECT-type E3 ubiquitin transferase
#2: Chemical ChemComp-TJQ / ethyl 5-[1,3-benzodioxol-5-ylmethyl(ethyl)carbamoyl]-2,4-dimethyl-1~{H}-pyrrole-3-carboxylate


Mass: 372.415 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H24N2O5 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 217 / 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: 2.47 Å3/Da / Density % sol: 50.22 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 1.5 M NaH2PO4/K2HPO4 pH 6.8, 100 mM NaOAc

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Mar 13, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.08→76.31 Å / Num. obs: 35457 / % possible obs: 99.9 % / Redundancy: 6.33 % / Rmerge(I) obs: 0.08 / Net I/σ(I): 17.68
Reflection shellResolution: 2.08→2.15 Å / Redundancy: 6.51 % / Rmerge(I) obs: 0.499 / Mean I/σ(I) obs: 3.72 / Num. unique obs: 675 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
BUSTER2.11.8refinement
XDSdata reduction
XSCALEdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1WAPI

Resolution: 2.08→43.27 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.902 / SU R Cruickshank DPI: 0.185 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.191 / SU Rfree Blow DPI: 0.168 / SU Rfree Cruickshank DPI: 0.165
RfactorNum. reflection% reflectionSelection details
Rfree0.259 1773 -RANDOM
Rwork0.2287 ---
obs0.2302 35456 99.9 %-
Displacement parametersBiso mean: 36.82 Å2
Baniso -1Baniso -2Baniso -3
1-5.7642 Å20 Å20 Å2
2---0.301 Å20 Å2
3----5.4632 Å2
Refine analyzeLuzzati coordinate error obs: 0.3 Å
Refinement stepCycle: LAST / Resolution: 2.08→43.27 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3090 0 32 217 3339
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0083202HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.854331HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1134SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes542HARMONIC5
X-RAY DIFFRACTIONt_it3202HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion388SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact2392SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion2.96
X-RAY DIFFRACTIONt_other_torsion17.42
LS refinement shellResolution: 2.08→2.09 Å
RfactorNum. reflection% reflection
Rfree0.3175 35 -
Rwork0.2764 --
obs0.2783 710 100 %

+
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