[English] 日本語
Yorodumi
- PDB-4rn1: Crystal structure of S39D HDAC8 in complex with a largazole analogue. -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4rn1
TitleCrystal structure of S39D HDAC8 in complex with a largazole analogue.
ComponentsHistone deacetylase 8
KeywordsHYDROLASE/HYDROLASE INHIBITOR / metalloenzyme / hydrolase / histone deacetylase / enzyme inhibitor complex / largazole analogue / thiol inhibitor / arginase/deacetylase fold / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


histone decrotonylase activity / histone deacetylase activity, hydrolytic mechanism / histone deacetylase / regulation of telomere maintenance / protein lysine deacetylase activity / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / mitotic sister chromatid cohesion / histone deacetylase activity / nuclear chromosome / Notch-HLH transcription pathway ...histone decrotonylase activity / histone deacetylase activity, hydrolytic mechanism / histone deacetylase / regulation of telomere maintenance / protein lysine deacetylase activity / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / mitotic sister chromatid cohesion / histone deacetylase activity / nuclear chromosome / Notch-HLH transcription pathway / histone deacetylase complex / Hsp70 protein binding / negative regulation of protein ubiquitination / Resolution of Sister Chromatid Cohesion / HDACs deacetylate histones / Hsp90 protein binding / regulation of protein stability / NOTCH1 Intracellular Domain Regulates Transcription / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Separation of Sister Chromatids / heterochromatin formation / chromatin organization / DNA-binding transcription factor binding / negative regulation of transcription by RNA polymerase II / nucleoplasm / metal ion binding / nucleus / cytoplasm
Similarity search - Function
Histone deacetylase / Histone deacetylase domain / Arginase; Chain A / : / Histone deacetylase family / Histone deacetylase domain / Histone deacetylase domain superfamily / Histone deacetylase domain / Ureohydrolase domain superfamily / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
IMIDAZOLE / : / Chem-L8G / Histone deacetylase 8
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.18 Å
AuthorsDecroos, C. / Christianson, D.W.
CitationJournal: Biochemistry / Year: 2015
Title: Variable Active Site Loop Conformations Accommodate the Binding of Macrocyclic Largazole Analogues to HDAC8.
Authors: Decroos, C. / Clausen, D.J. / Haines, B.E. / Wiest, O. / Williams, R.M. / Christianson, D.W.
History
DepositionOct 22, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 8, 2015Provider: repository / Type: Initial release
Revision 1.1Apr 22, 2015Group: Database references
Revision 1.2Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_auth_comp_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_atom_id / _pdbx_struct_conn_angle.ptnr2_label_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone deacetylase 8
B: Histone deacetylase 8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)87,94812
Polymers86,5202
Non-polymers1,42810
Water6,287349
1
A: Histone deacetylase 8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,0547
Polymers43,2601
Non-polymers7946
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Histone deacetylase 8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,8935
Polymers43,2601
Non-polymers6334
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)54.051, 85.124, 95.354
Angle α, β, γ (deg.)90.00, 100.21, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Histone deacetylase 8 / HD8


Mass: 43260.000 Da / Num. of mol.: 2 / Fragment: S39D HDAC8 / Mutation: S39D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HDAC8, HDACL1, CDA07 / Plasmid: pHD2-Xa-His / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q9BY41, histone deacetylase

-
Non-polymers , 6 types, 359 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical
ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: K
#4: Chemical ChemComp-L8G / (5R,8S,11S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-3-thia-7,10,14,20,21-pentaazatricyclo[14.3.1.1~2,5~]henicosa-1(20),2(21),16,18-tetraene-6,9,13-trione


Mass: 489.654 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H31N5O3S2
#5: Chemical ChemComp-IMD / IMIDAZOLE


Mass: 69.085 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H5N2
#6: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 349 / 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: 2.5 Å3/Da / Density % sol: 50.71 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.3
Details: 0.1 M Imidazole (pH=7.0), 4 mM tris(2-carboxyethyl)phosphine (TCEP), 13% PEG 3350, pH 7.3, VAPOR DIFFUSION, SITTING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X29A / Wavelength: 1.075 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Aug 1, 2014 / Details: mirrors
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.075 Å / Relative weight: 1
ReflectionResolution: 2.18→50 Å / Num. all: 44475 / Num. obs: 44473 / % possible obs: 100 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 6.2 % / Rmerge(I) obs: 0.124 / Net I/σ(I): 13
Reflection shellResolution: 2.18→2.26 Å / Redundancy: 6.1 % / Rmerge(I) obs: 0.811 / Mean I/σ(I) obs: 2.8 / Num. unique all: 4408 / % possible all: 100

-
Processing

Software
NameVersionClassification
CBASSdata collection
PHASERphasing
PHENIX(phenix.refine: dev_1833)refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3EWF

3ewf


Resolution: 2.18→43.113 Å / SU ML: 0.29 / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 22.48 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2125 2238 5.04 %random
Rwork0.1819 ---
obs0.1835 44415 99.8 %-
all-44485 --
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 36.08 Å2
Refinement stepCycle: LAST / Resolution: 2.18→43.113 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5561 0 83 349 5993
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0025835
X-RAY DIFFRACTIONf_angle_d0.6637938
X-RAY DIFFRACTIONf_dihedral_angle_d11.1122110
X-RAY DIFFRACTIONf_chiral_restr0.024878
X-RAY DIFFRACTIONf_plane_restr0.0031014
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.1795-2.22690.46021500.43762545X-RAY DIFFRACTION98
2.2269-2.27870.46661280.37822623X-RAY DIFFRACTION100
2.2787-2.33570.33851270.29782637X-RAY DIFFRACTION100
2.3357-2.39880.26481530.22112616X-RAY DIFFRACTION100
2.3988-2.46940.28061220.20132656X-RAY DIFFRACTION100
2.4694-2.54910.20791580.19052601X-RAY DIFFRACTION100
2.5491-2.64020.24431450.18512634X-RAY DIFFRACTION100
2.6402-2.74590.24861420.18292638X-RAY DIFFRACTION100
2.7459-2.87080.23631450.18822629X-RAY DIFFRACTION100
2.8708-3.02220.22031290.18542642X-RAY DIFFRACTION100
3.0222-3.21150.22141220.19042640X-RAY DIFFRACTION100
3.2115-3.45930.21281400.18222652X-RAY DIFFRACTION100
3.4593-3.80730.21971250.17192653X-RAY DIFFRACTION100
3.8073-4.35770.16031390.14072654X-RAY DIFFRACTION100
4.3577-5.48850.14791690.13432643X-RAY DIFFRACTION100
5.4885-43.12150.1451440.14372714X-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