[English] 日本語
Yorodumi
- PDB-6cee: Crystal structure of fragment 3-(1-Methyl-2-oxo-1,2-dihydroquinox... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cee
TitleCrystal structure of fragment 3-(1-Methyl-2-oxo-1,2-dihydroquinoxalin-3-yl)propionic acid bound in the ubiquitin binding pocket of the HDAC6 zinc-finger domain
ComponentsHistone deacetylase 6
KeywordsHYDROLASE / HISTONE DEACETYLASE / HDAC / HDAC6 / UBIQUITIN / STRUCTURAL GENOMICS CONSORTIUM / SGC
Function / homology
Function and homology information


negative regulation of hydrogen peroxide metabolic process / cellular response to topologically incorrect protein / polyubiquitinated misfolded protein transport / positive regulation of cellular response to oxidative stress / erythrocyte enucleation / negative regulation of aggrephagy / positive regulation of cholangiocyte proliferation / response to misfolded protein / negative regulation of oxidoreductase activity / regulation of microtubule-based movement ...negative regulation of hydrogen peroxide metabolic process / cellular response to topologically incorrect protein / polyubiquitinated misfolded protein transport / positive regulation of cellular response to oxidative stress / erythrocyte enucleation / negative regulation of aggrephagy / positive regulation of cholangiocyte proliferation / response to misfolded protein / negative regulation of oxidoreductase activity / regulation of microtubule-based movement / parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization / negative regulation of protein-containing complex disassembly / protein-containing complex disassembly / negative regulation of axon extension involved in axon guidance / regulation of establishment of protein localization / positive regulation of tubulin deacetylation / tubulin deacetylation / Cilium Assembly / regulation of autophagy of mitochondrion / peptidyl-lysine deacetylation / tubulin deacetylase activity / collateral sprouting / Transcriptional regulation by RUNX2 / lysosome localization / negative regulation of protein acetylation / misfolded protein binding / negative regulation of microtubule depolymerization / ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway / protein deacetylation / cilium disassembly / response to growth factor / dendritic spine morphogenesis / histone deacetylase / aggresome assembly / regulation of androgen receptor signaling pathway / protein lysine deacetylase activity / positive regulation of signaling receptor activity / cellular response to misfolded protein / aggresome / cellular response to parathyroid hormone stimulus / positive regulation of dendrite morphogenesis / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / regulation of fat cell differentiation / microtubule associated complex / negative regulation of gene expression, epigenetic / histone deacetylase activity / response to corticosterone / dynein complex binding / axonal transport of mitochondrion / Notch-HLH transcription pathway / positive regulation of epithelial cell migration / beta-tubulin binding / cell leading edge / response to dexamethasone / protein quality control for misfolded or incompletely synthesized proteins / RUNX2 regulates osteoblast differentiation / histone deacetylase complex / response to immobilization stress / alpha-tubulin binding / cilium assembly / HSF1 activation / polyubiquitin modification-dependent protein binding / regulation of macroautophagy / negative regulation of protein-containing complex assembly / inclusion body / axon cytoplasm / response to amphetamine / multivesicular body / positive regulation of synaptic transmission, glutamatergic / transcription corepressor binding / ciliary basal body / ubiquitin binding / regulation of autophagy / caveola / negative regulation of proteolysis / actin filament organization / Late endosomal microautophagy / intracellular protein transport / Hsp90 protein binding / protein destabilization / regulation of protein stability / tau protein binding / NOTCH1 Intracellular Domain Regulates Transcription / beta-catenin binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / autophagy / histone deacetylase binding / Aggrephagy / Chaperone Mediated Autophagy / cellular response to hydrogen peroxide / protein polyubiquitination / positive regulation of peptidyl-serine phosphorylation / actin binding / cellular response to heat / microtubule binding / perikaryon / microtubule / RNA polymerase II cis-regulatory region sequence-specific DNA binding / axon
Similarity search - Function
Ubiquitin Carboxyl-terminal Hydrolase-like zinc finger / Zinc finger, UBP-type / Zn-finger in ubiquitin-hydrolases and other protein / Zinc finger UBP-type profile. / Histone deacetylase family / Histone deacetylase domain / Histone deacetylase domain superfamily / Histone deacetylase domain / Zinc/RING finger domain, C3HC4 (zinc finger) / Ureohydrolase domain superfamily ...Ubiquitin Carboxyl-terminal Hydrolase-like zinc finger / Zinc finger, UBP-type / Zn-finger in ubiquitin-hydrolases and other protein / Zinc finger UBP-type profile. / Histone deacetylase family / Histone deacetylase domain / Histone deacetylase domain superfamily / Histone deacetylase domain / Zinc/RING finger domain, C3HC4 (zinc finger) / Ureohydrolase domain superfamily / Herpes Virus-1 / Zinc finger, RING/FYVE/PHD-type / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-EYM / Histone deacetylase 6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / Resolution: 1.55 Å
AuthorsHarding, R.J. / Halabelian, L. / Ferreira de Freitas, R. / Franzoni, I. / Ravichandran, M. / Lautens, M. / Santhakumar, V. / Schapira, M. / Bountra, C. / Edwards, A.M. ...Harding, R.J. / Halabelian, L. / Ferreira de Freitas, R. / Franzoni, I. / Ravichandran, M. / Lautens, M. / Santhakumar, V. / Schapira, M. / Bountra, C. / Edwards, A.M. / Arrowsmith, C.M. / Structural Genomics Consortium (SGC)
CitationJournal: J. Med. Chem. / Year: 2018
Title: Identification and Structure-Activity Relationship of HDAC6 Zinc-Finger Ubiquitin Binding Domain Inhibitors.
Authors: Ferreira de Freitas, R. / Harding, R.J. / Franzoni, I. / Ravichandran, M. / Mann, M.K. / Ouyang, H. / Lautens, M. / Santhakumar, V. / Arrowsmith, C.H. / Schapira, M.
History
DepositionFeb 11, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 28, 2018Provider: repository / Type: Initial release
Revision 1.1May 16, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2May 30, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone deacetylase 6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)12,3619
Polymers11,9331
Non-polymers4288
Water1,56787
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area5640 Å2
MethodPISA
Unit cell
Length a, b, c (Å)40.720, 44.110, 55.910
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Histone deacetylase 6 / HD6


Mass: 11932.607 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HDAC6, KIAA0901, JM21 / Plasmid: pET28-lic / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (DE3) codon plus / References: UniProt: Q9UBN7, histone deacetylase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-EYM / 3-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)propanoic acid


Mass: 232.235 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H12N2O3
#4: Chemical
ChemComp-UNX / UNKNOWN ATOM OR ION


Num. of mol.: 4 / Source method: obtained synthetically
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 87 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.09 Å3/Da / Density % sol: 41.07 % / Mosaicity: 0 °
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 4.6
Details: 2 M Na-formate, 0.2 M Na-acetate pH4.6, 5 % ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.54178 Å
DetectorType: RIGAKU SATURN A200 / Detector: CCD / Date: Aug 24, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 1.55→30 Å / Num. obs: 15166 / % possible obs: 100 % / Redundancy: 6.7 % / CC1/2: 1 / Rmerge(I) obs: 0.037 / Rpim(I) all: 0.015 / Rrim(I) all: 0.04 / Net I/σ(I): 40.5 / Num. measured all: 101184 / Scaling rejects: 3
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.55-1.5860.23146307660.9670.1020.2538.1100
8.49-29.925.20.02159011310.010.024102.198.2

-
Processing

Software
NameVersionClassification
REFMAC5.8.0189refinement
Aimless0.6.2data scaling
PDB_EXTRACT3.24data extraction
xia2data reduction
RefinementStarting model: pdbid 5KH3

5kh3


Resolution: 1.55→30 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.959 / SU B: 1.024 / SU ML: 0.038 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.069 / ESU R Free: 0.067 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: Users of this crystal structure: verify our intepretion of the electron density. Amplitudes and unmerged intensities are included with this deposition. Diffraction images will be deposited ...Details: Users of this crystal structure: verify our intepretion of the electron density. Amplitudes and unmerged intensities are included with this deposition. Diffraction images will be deposited at a later date in a public repository. Geometry restraints for the ligand were prepared with GRADE.
RfactorNum. reflection% reflectionSelection details
Rfree0.1694 728 4.8 %RANDOM
Rwork0.153 ---
obs0.1538 14437 99.89 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 36.3 Å2 / Biso mean: 12.359 Å2 / Biso min: 6.93 Å2
Baniso -1Baniso -2Baniso -3
1--0.05 Å20 Å20 Å2
2--0.7 Å2-0 Å2
3----0.64 Å2
Refinement stepCycle: final / Resolution: 1.55→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms777 0 24 87 888
Biso mean--19.92 22.09 -
Num. residues----100
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.019845
X-RAY DIFFRACTIONr_bond_other_d0.0020.02700
X-RAY DIFFRACTIONr_angle_refined_deg1.6751.9161161
X-RAY DIFFRACTIONr_angle_other_deg1.1723.011621
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.5855101
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.63324.32437
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.99415110
X-RAY DIFFRACTIONr_dihedral_angle_4_deg23.323151
X-RAY DIFFRACTIONr_chiral_restr0.1240.2118
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.0211012
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02170
LS refinement shellResolution: 1.55→1.59 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.163 54 -
Rwork0.154 1050 -
all-1104 -
obs--99.82 %

+
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://pdbjlvh1.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