[English] 日本語
Yorodumi
- PDB-5wbn: Crystal structure of fragment 3-(3-Benzyl-2-oxo-2H-[1,2,4]triazin... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5wbn
TitleCrystal structure of fragment 3-(3-Benzyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)propanoic acid bound in the ubiquitin binding pocket of the HDAC6 zinc-finger domain
ComponentsHistone deacetylase 6
Keywordshydrolase/hydrolase inhibitor / HISTONE DEACETYLASE / HDAC / HDAC6 / FRAGMENT SCREENING / STRUCTURAL GENOMICS CONSORTIUM / SGC / hydrolase-hydrolase inhibitor complex
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 / positive regulation of protein oligomerization / negative regulation of axon extension involved in axon guidance ...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 / positive regulation of protein oligomerization / negative regulation of axon extension involved in axon guidance / regulation of microtubule-based movement / type 2 mitophagy / negative regulation of protein-containing complex disassembly / peroxidase inhibitor activity / regulation of establishment of protein localization / regulation of autophagy of mitochondrion / protein-containing complex disassembly / tubulin deacetylation / Cilium Assembly / collateral sprouting / tubulin deacetylase activity / Transcriptional regulation by RUNX2 / lysosome localization / negative regulation of microtubule depolymerization / positive regulation of dendrite morphogenesis / ATPase inhibitor activity / cilium disassembly / misfolded protein binding / ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway / positive regulation of type 2 mitophagy / histone H4K16 deacetylase activity, hydrolytic mechanism / histone H4K5 deacetylase activity, hydrolytic mechanism / histone H4K8 deacetylase activity, hydrolytic mechanism / histone H3K4 deacetylase activity, hydrolytic mechanism / histone H3K14 deacetylase activity, hydrolytic mechanism / dendritic spine morphogenesis / histone H4K12 deacetylase activity, hydrolytic mechanism / protein deacetylation / histone H3K9 deacetylase activity, hydrolytic mechanism / aggresome assembly / regulation of androgen receptor signaling pathway / regulation of mitochondrion organization / cellular response to misfolded protein / Transferases; Acyltransferases; Aminoacyltransferases / regulation of fat cell differentiation / protein lysine deacetylase activity / microtubule associated complex / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / aggresome / cellular response to parathyroid hormone stimulus / response to corticosterone / histone deacetylase activity / positive regulation of intracellular estrogen receptor signaling pathway / Notch-HLH transcription pathway / negative regulation of gene expression, epigenetic / axonal transport of mitochondrion / dynein complex binding / beta-tubulin binding / protein quality control for misfolded or incompletely synthesized proteins / RUNX2 regulates osteoblast differentiation / cell leading edge / response to dexamethasone / histone deacetylase complex / response to immobilization stress / positive regulation of epithelial cell migration / cilium assembly / polyubiquitin modification-dependent protein binding / alpha-tubulin binding / regulation of macroautophagy / HSF1 activation / negative regulation of protein-containing complex assembly / inclusion body / negative regulation of proteolysis / axon cytoplasm / multivesicular body / response to amphetamine / positive regulation of synaptic transmission, glutamatergic / epigenetic regulation of gene expression / ubiquitin binding / actin filament organization / transcription corepressor binding / intracellular protein transport / Hsp90 protein binding / Late endosomal microautophagy / protein destabilization / regulation of protein stability / beta-catenin binding / caveola / tau protein binding / NOTCH1 Intracellular Domain Regulates Transcription / cellular response to hydrogen peroxide / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / epidermal growth factor receptor signaling pathway / histone deacetylase binding / Chaperone Mediated Autophagy / protein polyubiquitination / Aggrephagy / actin binding / cellular response to heat
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) ...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) / Herpes Virus-1 / Ureohydrolase domain superfamily / Zinc finger, RING/FYVE/PHD-type / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-9ZV / ACETATE ION / FORMIC ACID / Protein deacetylase HDAC6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / Resolution: 1.64 Å
AuthorsHarding, R.J. / Walker, J.R. / Ferreira de Freitas, R. / Ravichandran, M. / Santhakumar, V. / Schapira, M. / Bountra, C. / Edwards, A.M. / Arrowsmith, C.H.
CitationJournal: To be published
Title: Crystal structure of fragment 3-(3-Benzyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)propanoic acid bound in the ubiquitin binding pocket of the HDAC6 zinc-finger domain
Authors: Harding, R.J. / Walker, J.R. / Ferreira de Freitas, R. / Ravichandran, M. / Santhakumar, V. / Schapira, M. / Bountra, C. / Edwards, A.M. / Arrowsmith, C.H.
History
DepositionJun 29, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 2, 2017Provider: repository / Type: Initial release
Revision 1.1Mar 13, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
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)16,26519
Polymers11,9331
Non-polymers4,33218
Water2,666148
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)40.850, 43.740, 55.760
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#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-CodonPlus(DE3)-RIL / References: UniProt: Q9UBN7, histone deacetylase

-
Non-polymers , 7 types, 166 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-9ZV / 3-(3-benzyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)propanoic acid


Mass: 360.366 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H16N4O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-UNX / UNKNOWN ATOM OR ION


Mass: 435.516 Da / Num. of mol.: 8 / Source method: obtained synthetically
#5: Chemical ChemComp-FMT / FORMIC ACID


Mass: 46.025 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: CH2O2
#6: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#7: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H3O2
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 148 / 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: 2M Na-formate, 0.2M 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: Dec 17, 2015 / Details: A200
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 1.64→32.62 Å / Num. obs: 11842 / % possible obs: 100 % / Redundancy: 6.8 % / CC1/2: 0.998 / Rmerge(I) obs: 0.089 / Rpim(I) all: 0.037 / Rrim(I) all: 0.097 / Net I/σ(I): 21.2 / Num. measured all: 80148 / Scaling rejects: 0
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsCC1/2Rpim(I) allRrim(I) all% possible all
1.69-1.736.60.3610.9320.150.392100
7.56-32.625.50.02410.0110.02698.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0158refinement
Aimless0.5.31data scaling
PDB_EXTRACT3.22data extraction
XDSdata reduction
RefinementResolution: 1.64→34.44 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.953 / SU B: 1.449 / SU ML: 0.05 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.086 / ESU R Free: 0.087 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1675 564 4.8 %RANDOM
Rwork0.1319 ---
obs0.1336 11278 93.63 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 51.62 Å2 / Biso mean: 9.104 Å2 / Biso min: 1.78 Å2
Baniso -1Baniso -2Baniso -3
1--0.09 Å20 Å20 Å2
2--0.51 Å2-0 Å2
3----0.41 Å2
Refinement stepCycle: final / Resolution: 1.64→34.44 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms801 0 56 149 1006
Biso mean--14.44 21.65 -
Num. residues----103
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.019917
X-RAY DIFFRACTIONr_bond_other_d0.0030.02754
X-RAY DIFFRACTIONr_angle_refined_deg1.6971.9261256
X-RAY DIFFRACTIONr_angle_other_deg1.1593.0091751
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2745110
X-RAY DIFFRACTIONr_dihedral_angle_2_deg41.77924.7540
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.28815119
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.354151
X-RAY DIFFRACTIONr_chiral_restr0.1180.2124
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0211163
X-RAY DIFFRACTIONr_gen_planes_other0.0030.02186
LS refinement shellResolution: 1.645→1.687 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.171 14 -
Rwork0.182 227 -
all-241 -
obs--26.22 %

+
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