[English] 日本語
Yorodumi
- PDB-8g1q: Co-crystal structure of Compound 1 in complex with the bromodomai... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8g1q
TitleCo-crystal structure of Compound 1 in complex with the bromodomain of human SMARCA4 and pVHL:ElonginC:ElonginB
Components
  • Elongin-B
  • Elongin-C
  • Transcription activator BRG1
  • von Hippel-Lindau disease tumor suppressor
KeywordsGENE REGULATION / Ternary Complex / PROTACs / TRANSCRIPTION
Function / homology
Function and homology information


positive regulation of glucose mediated signaling pathway / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / bBAF complex / neural retina development / regulation of cellular response to hypoxia / npBAF complex / negative regulation of androgen receptor signaling pathway / nBAF complex / EGR2 and SOX10-mediated initiation of Schwann cell myelination / nucleosome array spacer activity ...positive regulation of glucose mediated signaling pathway / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / bBAF complex / neural retina development / regulation of cellular response to hypoxia / npBAF complex / negative regulation of androgen receptor signaling pathway / nBAF complex / EGR2 and SOX10-mediated initiation of Schwann cell myelination / nucleosome array spacer activity / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / GBAF complex / regulation of G0 to G1 transition / Tat protein binding / RNA polymerase I preinitiation complex assembly / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / RSC-type complex / ATP-dependent chromatin remodeler activity / host-mediated activation of viral transcription / regulation of nucleotide-excision repair / Replication of the SARS-CoV-1 genome / nucleosome disassembly / VCB complex / Cul5-RING ubiquitin ligase complex / regulation of mitotic metaphase/anaphase transition / SWI/SNF complex / Cul2-RING ubiquitin ligase complex / positive regulation of T cell differentiation / intracellular membraneless organelle / nuclear androgen receptor binding / positive regulation of double-strand break repair / SUMOylation of ubiquitinylation proteins / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / positive regulation of stem cell population maintenance / Regulation of MITF-M-dependent genes involved in pigmentation / regulation of G1/S transition of mitotic cell cycle / 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 / positive regulation of signal transduction by p53 class mediator / negative regulation of cell differentiation / ATP-dependent activity, acting on DNA / positive regulation of Wnt signaling pathway / positive regulation of myoblast differentiation / 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 / Chromatin modifying enzymes / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / DNA polymerase binding / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / transcription initiation-coupled chromatin remodeling / Interleukin-7 signaling / protein serine/threonine kinase binding / negative regulation of autophagy / transcription corepressor binding / transcription coregulator binding / positive regulation of cell differentiation / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / Formation of the beta-catenin:TCF transactivating complex / helicase activity / negative regulation of cell growth / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / kinetochore / positive regulation of miRNA transcription / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / Regulation of expression of SLITs and ROBOs / RMTs methylate histone arginines / nuclear matrix / fibrillar center / cell morphogenesis / ubiquitin-protein transferase activity / p53 binding / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / nervous system development / positive regulation of cold-induced thermogenesis / Neddylation / microtubule cytoskeleton / regulation of gene expression / protein-containing complex assembly / Replication of the SARS-CoV-2 genome / ubiquitin-dependent protein catabolic process / histone binding
Similarity search - Function
SWI/SNF complex subunit BRG1 / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / BRK domain / BRK domain / BRK domain superfamily / domain in transcription and CHROMO domain helicases / Elongin C; Chain C, domain 1 / Glutamine-Leucine-Glutamine, QLQ / QLQ ...SWI/SNF complex subunit BRG1 / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / BRK domain / BRK domain / BRK domain superfamily / domain in transcription and CHROMO domain helicases / Elongin C; Chain C, domain 1 / Glutamine-Leucine-Glutamine, QLQ / QLQ / QLQ domain profile. / QLQ / Snf2-ATP coupling, chromatin remodelling complex / Snf2, ATP coupling domain / Snf2-ATP coupling, chromatin remodelling complex / domain in helicases and associated with SANT domains / 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 / HSA domain / Helicase/SANT-associated domain / HSA domain profile. / Elongin-C / Elongin B / Potassium Channel Kv1.1; Chain A / Potassium Channel Kv1.1; Chain A / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / : / SNF2-like, N-terminal domain superfamily / SNF2, N-terminal / SNF2-related domain / SKP1/BTB/POZ domain superfamily / Helicase conserved C-terminal domain / 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 / helicase superfamily c-terminal domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Ubiquitin-like domain superfamily / Immunoglobulin-like / Sandwich / P-loop containing nucleoside triphosphate hydrolase / 2-Layer Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
DI(HYDROXYETHYL)ETHER / Chem-YHB / von Hippel-Lindau disease tumor suppressor / SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.73 Å
AuthorsGhimire Rijal, S. / Wurz, R.P. / Vaish, A.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2023
Title: Affinity and cooperativity modulate ternary complex formation to drive targeted protein degradation.
Authors: Wurz, R.P. / Rui, H. / Dellamaggiore, K. / Ghimire-Rijal, S. / Choi, K. / Smither, K. / Amegadzie, A. / Chen, N. / Li, X. / Banerjee, A. / Chen, Q. / Mohl, D. / Vaish, A.
History
DepositionFeb 2, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 26, 2023Provider: repository / Type: Initial release
Revision 1.1Aug 30, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _pdbx_initial_refinement_model.type

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
H: Transcription activator BRG1
A: Elongin-B
B: Elongin-C
C: von Hippel-Lindau disease tumor suppressor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,7687
Polymers55,8204
Non-polymers9483
Water724
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)158.163, 158.163, 44.857
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number171
Space group name H-MP62

-
Components

-
Protein , 4 types, 4 molecules HABC

#1: Protein Transcription activator BRG1 / ATP-dependent helicase SMARCA4 / BRG1-associated factor 190A / BAF190A / Mitotic growth and ...ATP-dependent helicase SMARCA4 / BRG1-associated factor 190A / BAF190A / Mitotic growth and transcription activator / Protein BRG-1 / Protein brahma homolog 1 / SNF2-beta / SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4


Mass: 14525.742 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SMARCA4, BAF190A, BRG1, SNF2B, SNF2L4 / Production host: Escherichia coli (E. coli)
References: UniProt: P51532, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#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.: 1
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.: 1
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 von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 18702.291 Da / Num. of mol.: 1
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

-
Non-polymers , 4 types, 7 molecules

#5: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#6: Chemical ChemComp-YHB / N-(2-{4-[(6M)-3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl}pyridine-4-carbonyl)-3-methyl-L-valyl-(4R)-4-hydroxy-N-{(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide


Mass: 818.986 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C43H50N10O5S
#7: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 4 / 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: 2.77 Å3/Da / Density % sol: 55.67 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: PEG 300 0.1M Bis-Tris 6.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: May 20, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.73→45.66 Å / Num. obs: 6928 / % possible obs: 99.88 % / Redundancy: 10.8 % / CC1/2: 0.99 / Rrim(I) all: 0.366 / Net I/σ(I): 7.7
Reflection shellResolution: 3.73→4.17 Å / Redundancy: 10.1 % / Rmerge(I) obs: 0.065 / Num. unique obs: 6944 / CC1/2: 0.99

-
Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.73→45.66 Å / SU ML: 0.59 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 33.85 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.3258 346 4.99 %
Rwork0.2347 --
obs0.2395 6928 99.88 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.73→45.66 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3399 0 67 4 3470
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0043558
X-RAY DIFFRACTIONf_angle_d0.7554825
X-RAY DIFFRACTIONf_dihedral_angle_d14.289482
X-RAY DIFFRACTIONf_chiral_restr0.046542
X-RAY DIFFRACTIONf_plane_restr0.007622
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.73-4.70.36011690.25353236X-RAY DIFFRACTION100
4.7-45.660.30421770.22223346X-RAY DIFFRACTION100

+
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