[English] 日本語
Yorodumi
- PDB-9d4b: Discovery of SMD-3236, a Potent, Highly Selective and Efficacious... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9d4b
TitleDiscovery of SMD-3236, a Potent, Highly Selective and Efficacious SMARCA2 Degrader for the Treatment of SMARC4-Deficient Human Cancers
Components
  • Elongin-B
  • Elongin-C
  • Probable global transcription activator SNF2L2
  • von Hippel-Lindau disease tumor suppressor
KeywordsTRANSCRIPTION / Cancer / Protein Degrader
Function / homology
Function and homology information


regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / RSC-type complex / Replication of the SARS-CoV-1 genome / VCB complex / Cul5-RING ubiquitin ligase complex ...regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / RSC-type complex / Replication of the SARS-CoV-1 genome / VCB complex / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / intracellular membraneless organelle / SUMOylation of ubiquitinylation proteins / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / negative regulation of transcription elongation by RNA polymerase II / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / negative regulation of signal transduction / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / ubiquitin-like ligase-substrate adaptor activity / Formation of HIV elongation complex in the absence of HIV Tat / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / protein serine/threonine kinase binding / negative regulation of autophagy / transcription corepressor binding / positive regulation of cell differentiation / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / cell morphogenesis / ubiquitin-protein transferase activity / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / microtubule cytoskeleton / regulation of gene expression / protein-containing complex assembly / Replication of the SARS-CoV-2 genome / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / cellular response to hypoxia / DNA-binding transcription factor binding / molecular adaptor activity / amyloid fibril formation / proteasome-mediated ubiquitin-dependent protein catabolic process / protein stabilization / protein ubiquitination / cilium / chromatin remodeling / negative regulation of cell population proliferation / negative regulation of gene expression / ubiquitin protein ligase binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / enzyme binding / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / mitochondrion / proteolysis / nucleoplasm / nucleus / plasma membrane / cytosol
Similarity search - Function
Remodelling complex subunit Rsc/polybromo / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain / Elongin-C ...Remodelling complex subunit Rsc/polybromo / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain / Elongin-C / Elongin B / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / SKP1/BTB/POZ domain superfamily / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily
Similarity search - Domain/homology
: / SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 / von Hippel-Lindau disease tumor suppressor / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.3 Å
AuthorsStrickland, C.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: To Be Published
Title: Discovery of SMD-3236, a Potent, Highly Selective and Efficacious SMARCA2 Degrader for the Treatment of SMARC4-Deficient Human Cancers
Authors: Strickland, C.
History
DepositionAug 12, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 20, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: von Hippel-Lindau disease tumor suppressor
B: Elongin-B
C: Elongin-C
D: von Hippel-Lindau disease tumor suppressor
E: Elongin-B
F: Elongin-C
G: Probable global transcription activator SNF2L2
H: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)113,36710
Polymers111,1758
Non-polymers2,1922
Water00
1
A: von Hippel-Lindau disease tumor suppressor
B: Elongin-B
C: Elongin-C
G: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,6835
Polymers55,5884
Non-polymers1,0961
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
D: von Hippel-Lindau disease tumor suppressor
E: Elongin-B
F: Elongin-C
H: Probable global transcription activator SNF2L2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,6835
Polymers55,5884
Non-polymers1,0961
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)93.130, 132.010, 210.700
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 18615.215 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli (E. coli) / References: UniProt: P40337
#2: Protein Elongin-B / EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / ...EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / Transcription elongation factor B polypeptide 2


Mass: 11748.406 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15370
#3: Protein Elongin-C / EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / ...EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / Transcription elongation factor B polypeptide 1


Mass: 10843.420 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15369
#4: Protein Probable global transcription activator SNF2L2 / cDNA FLJ61143 / highly similar to Probable global transcription activator SNF2L2


Mass: 14380.542 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SMARCA2 / Production host: Escherichia coli (E. coli) / References: UniProt: B4DNT1
#5: Chemical ChemComp-A1A1U / (4R)-1-[(2S)-2-{4-[(1S,4S)-4-({4-[(12'S)-4'-chloro-5'-oxo-5'H-spiro[cyclohexane-1,7'-indolo[1,2-a]quinazolin]-10'-yl]piperidin-1-yl}methyl)cyclohexyl]-1H-1,2,3-triazol-1-yl}-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1R)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-2-(morpholin-4-yl)ethyl]-L-prolinamide


Mass: 1095.830 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C61H75ClN10O5S / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.91 Å3/Da / Density % sol: 57.77 %
Crystal growTemperature: 281.15 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 0.25 M Calcium acetate 0.1 M Sodium cacodylate pH 5.5 8% w/v PEG 8000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL45XU / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 18, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.3→48.1 Å / Num. obs: 19935 / % possible obs: 100 % / Redundancy: 13.5 % / CC1/2: 0.994 / Rmerge(I) obs: 0.285 / Rpim(I) all: 0.079 / Rrim(I) all: 0.296 / Χ2: 1 / Net I/σ(I): 10.4 / Num. measured all: 269614
Reflection shellResolution: 3.3→3.56 Å / % possible obs: 100 % / Redundancy: 13.1 % / Rmerge(I) obs: 1.2 / Num. measured all: 53265 / Num. unique obs: 4058 / CC1/2: 0.812 / Rpim(I) all: 0.342 / Rrim(I) all: 1.248 / Χ2: 0.96 / Net I/σ(I) obs: 2.6

-
Processing

Software
NameVersionClassification
REFMAC5.8.0403refinement
Aimlessdata scaling
XDSdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.3→48.1 Å / Cor.coef. Fo:Fc: 0.926 / Cor.coef. Fo:Fc free: 0.86 / SU B: 29.228 / SU ML: 0.475 / Cross valid method: THROUGHOUT / ESU R Free: 0.601 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.28581 1014 5.1 %RANDOM
Rwork0.20734 ---
obs0.21124 18919 99.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 78.343 Å2
Baniso -1Baniso -2Baniso -3
1--0.14 Å2-0 Å20 Å2
2--0.55 Å20 Å2
3----0.41 Å2
Refinement stepCycle: 1 / Resolution: 3.3→48.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7272 0 156 0 7428
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0127604
X-RAY DIFFRACTIONr_bond_other_d0.0010.0167338
X-RAY DIFFRACTIONr_angle_refined_deg1.3851.67110316
X-RAY DIFFRACTIONr_angle_other_deg0.431.57216950
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.0045890
X-RAY DIFFRACTIONr_dihedral_angle_2_deg7.539566
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.6101342
X-RAY DIFFRACTIONr_chiral_restr0.0620.21154
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.028698
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021704
X-RAY DIFFRACTIONr_mcbond_it7.1717.6183590
X-RAY DIFFRACTIONr_mcbond_other7.1717.6183590
X-RAY DIFFRACTIONr_mcangle_it11.37413.6694470
X-RAY DIFFRACTIONr_mcangle_other11.37313.674471
X-RAY DIFFRACTIONr_scbond_it7.0898.0224014
X-RAY DIFFRACTIONr_scbond_other7.0888.0244015
X-RAY DIFFRACTIONr_scangle_other11.4614.4825847
X-RAY DIFFRACTIONr_long_range_B_refined15.95274.858538
X-RAY DIFFRACTIONr_long_range_B_other15.95174.868539
LS refinement shellResolution: 3.3→3.385 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.34 83 -
Rwork0.269 1360 -
obs--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