[English] 日本語
Yorodumi
- PDB-8frq: LSD1-CoREST in complex with T14, long soaking -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8frq
TitleLSD1-CoREST in complex with T14, long soaking
Components
  • Lysine-specific histone demethylase 1A
  • REST corepressor 1
KeywordsOXIDOREDUCTASE/INHIBITOR / Epigenetics / Histone demethylase / Drug resistance / Covalent inhibitor / OXIDOREDUCTASE / OXIDOREDUCTASE-INHIBITOR complex
Function / homology
Function and homology information


positive regulation of megakaryocyte differentiation / guanine metabolic process / : / protein demethylation / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / demethylase activity / telomeric repeat-containing RNA binding / histone H3K4 demethylase activity / muscle cell development ...positive regulation of megakaryocyte differentiation / guanine metabolic process / : / protein demethylation / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / demethylase activity / telomeric repeat-containing RNA binding / histone H3K4 demethylase activity / muscle cell development / neuron maturation / positive regulation of neural precursor cell proliferation / regulation of androgen receptor signaling pathway / MRF binding / DNA repair complex / nuclear androgen receptor binding / regulation of double-strand break repair via homologous recombination / DNA repair-dependent chromatin remodeling / positive regulation of neuroblast proliferation / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of stem cell proliferation / negative regulation of DNA binding / histone H3K9 demethylase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / histone deacetylase complex / positive regulation of cell size / histone demethylase activity / positive regulation of epithelial to mesenchymal transition / response to fungicide / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / cellular response to cAMP / transcription repressor complex / erythrocyte differentiation / nuclear receptor coactivator activity / negative regulation of protein binding / positive regulation of protein ubiquitination / Regulation of PTEN gene transcription / HDACs deacetylate histones / promoter-specific chromatin binding / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / negative regulation of DNA-binding transcription factor activity / HDMs demethylate histones / cellular response to gamma radiation / cerebral cortex development / positive regulation of neuron projection development / transcription corepressor activity / cellular response to UV / p53 binding / flavin adenine dinucleotide binding / chromatin organization / regulation of protein localization / positive regulation of cold-induced thermogenesis / Factors involved in megakaryocyte development and platelet production / DNA-binding transcription factor binding / Estrogen-dependent gene expression / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / Potential therapeutics for SARS / chromosome, telomeric region / transcription coactivator activity / oxidoreductase activity / chromatin remodeling / negative regulation of gene expression / negative regulation of DNA-templated transcription / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / nucleus
Similarity search - Function
: / Helical region in REST corepressor / : / ELM2 domain / ELM2 domain / ELM2 domain profile. / ELM2 / Histone lysine-specific demethylase / SWIRM domain / SWIRM domain ...: / Helical region in REST corepressor / : / ELM2 domain / ELM2 domain / ELM2 domain profile. / ELM2 / Histone lysine-specific demethylase / SWIRM domain / SWIRM domain / SWIRM domain profile. / : / SANT domain profile. / SANT domain / Amine oxidase / Flavin containing amine oxidoreductase / Myb-like DNA-binding domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / Homeobox-like domain superfamily / FAD/NAD(P)-binding domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
: / Lysine-specific histone demethylase 1A / REST corepressor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.89 Å
AuthorsCaroli, J. / Mattevi, A.
Funding support Italy, 1items
OrganizationGrant numberCountry
Italian Association for Cancer ResearchIG19808 Italy
CitationJournal: to be published
Title: Distal drug resistance mutations promote covalent inhibitor-adduct Grob fragmentation in LSD1
Authors: Caroli, J. / Mattevi, A.
History
DepositionJan 8, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 7, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Lysine-specific histone demethylase 1A
B: REST corepressor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)112,5723
Polymers111,5112
Non-polymers1,0611
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5360 Å2
ΔGint-40 kcal/mol
Surface area37830 Å2
MethodPISA
Unit cell
Length a, b, c (Å)119.331, 179.769, 234.464
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein Lysine-specific histone demethylase 1A / BRAF35-HDAC complex protein BHC110 / Flavin-containing amine oxidase domain-containing protein 2 / ...BRAF35-HDAC complex protein BHC110 / Flavin-containing amine oxidase domain-containing protein 2 / [histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A


Mass: 95051.633 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KDM1A, AOF2, KDM1, KIAA0601, LSD1 / Production host: Escherichia coli (E. coli)
References: UniProt: O60341, [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase
#2: Protein REST corepressor 1 / Protein CoREST


Mass: 16459.742 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RCOR1, KIAA0071, RCOR / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UKL0
#3: Chemical ChemComp-XF6 / [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2R,3S,4S)-5-[(4aS)-7,8-dimethyl-5-(3-{4-[(5-methyl-1,3,4-thiadiazol-2-yl)carbamoyl]phenyl}propanoyl)-2,4-dioxo-3,4,4a,5-tetrahydrobenzo[g]pteridin-10(2H)-yl]-2,3,4-trihydroxypentyl dihydrogen diphosphate (non-preferred name)


Mass: 1060.876 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C40H46N12O17P2S / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 5.64 Å3/Da / Density % sol: 78.18 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: 1.2 Na/K Tartrate, 100 mM ADA pH 6.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.965459 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jun 22, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.965459 Å / Relative weight: 1
ReflectionResolution: 2.89→48.71 Å / Num. obs: 54900 / % possible obs: 97.1 % / Redundancy: 4 % / CC1/2: 0.809 / Rmerge(I) obs: 0.152 / Rpim(I) all: 0.096 / Rrim(I) all: 0.182 / Χ2: 1.03 / Net I/σ(I): 8.5 / Num. measured all: 221726
Reflection shellResolution: 2.89→2.97 Å / % possible obs: 98.8 % / Redundancy: 4.3 % / Rmerge(I) obs: 1.172 / Num. measured all: 19375 / Num. unique obs: 4539 / CC1/2: 0.374 / Rpim(I) all: 0.648 / Rrim(I) all: 1.349 / Χ2: 0.91 / Net I/σ(I) obs: 1.5

-
Processing

Software
NameVersionClassification
Aimlessdata scaling
PHENIX1.18.2refinement
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.89→48.71 Å / SU ML: 0.42 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2409 1975 3.64 %
Rwork0.2175 --
obs0.2183 54273 95.71 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.89→48.71 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6293 0 72 0 6365
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0116580
X-RAY DIFFRACTIONf_angle_d1.4788941
X-RAY DIFFRACTIONf_dihedral_angle_d11.671980
X-RAY DIFFRACTIONf_chiral_restr0.071995
X-RAY DIFFRACTIONf_plane_restr0.0091150
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.89-2.960.39061440.35983763X-RAY DIFFRACTION98
2.96-3.040.35221420.33343781X-RAY DIFFRACTION98
3.04-3.130.36931450.32313807X-RAY DIFFRACTION98
3.13-3.230.37791380.31443686X-RAY DIFFRACTION96
3.23-3.350.36591390.30463736X-RAY DIFFRACTION97
3.35-3.480.29871290.32273447X-RAY DIFFRACTION89
3.48-3.640.2771400.26663663X-RAY DIFFRACTION94
3.64-3.830.2741370.23913588X-RAY DIFFRACTION93
3.83-4.070.24281350.21883666X-RAY DIFFRACTION94
4.07-4.390.17941440.17313800X-RAY DIFFRACTION97
4.39-4.830.17171450.15973817X-RAY DIFFRACTION97
4.83-5.530.21061450.17333823X-RAY DIFFRACTION97
5.53-6.960.21881440.19123823X-RAY DIFFRACTION97
6.96-48.710.18211480.16473898X-RAY DIFFRACTION95

+
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