[English] 日本語
Yorodumi
- PDB-7zyu: HDAC6 ZnF domain inhibitor - DARPin (Designed Ankyrin repeat prot... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7zyu
TitleHDAC6 ZnF domain inhibitor - DARPin (Designed Ankyrin repeat protein) F10
Components
  • Designed Ankyrin repeat protein F10
  • Histone deacetylase 6
KeywordsDE NOVO PROTEIN / Darpin / zinc finger
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 / 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 / positive regulation of RIG-I signaling pathway ...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 / 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 / positive regulation of RIG-I signaling pathway / type 2 mitophagy / negative regulation of protein-containing complex disassembly / peroxidase inhibitor activity / erythrocyte enucleation / regulation of autophagy of mitochondrion / Cilium Assembly / regulation of microtubule-based movement / tubulin deacetylation / protein-containing complex disassembly / regulation of establishment of protein localization / collateral sprouting / Transcriptional regulation by RUNX2 / tubulin deacetylase activity / negative regulation of microtubule depolymerization / lysosome localization / positive regulation of dendrite morphogenesis / ATPase inhibitor activity / cilium disassembly / histone deacetylase activity, hydrolytic mechanism / misfolded protein binding / ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway / dendritic spine morphogenesis / positive regulation of type 2 mitophagy / protein deacetylation / aggresome assembly / regulation of androgen receptor signaling pathway / regulation of mitochondrion organization / Transferases; Acyltransferases; Aminoacyltransferases / cellular response to misfolded protein / regulation of fat cell differentiation / protein lysine deacetylase activity / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / aggresome / histone deacetylase activity / microtubule associated complex / cellular response to parathyroid hormone stimulus / response to corticosterone / positive regulation of intracellular estrogen receptor signaling pathway / response to dexamethasone / Notch-HLH transcription pathway / negative regulation of gene expression, epigenetic / axonal transport of mitochondrion / RUNX2 regulates osteoblast differentiation / histone deacetylase complex / cell leading edge / response to immobilization stress / dynein complex binding / protein quality control for misfolded or incompletely synthesized proteins / positive regulation of epithelial cell migration / polyubiquitin modification-dependent protein binding / cilium assembly / regulation of macroautophagy / HSF1 activation / positive regulation of synaptic transmission, glutamatergic / alpha-tubulin binding / negative regulation of protein-containing complex assembly / beta-tubulin binding / negative regulation of proteolysis / multivesicular body / inclusion body / axon cytoplasm / antiviral innate immune response / epigenetic regulation of gene expression / actin filament organization / response to amphetamine / ubiquitin binding / transcription corepressor binding / intracellular protein transport / Hsp90 protein binding / Late endosomal microautophagy / beta-catenin binding / protein destabilization / regulation of protein stability / caveola / NOTCH1 Intracellular Domain Regulates Transcription / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / tau protein binding / histone deacetylase binding / epidermal growth factor receptor signaling pathway / cellular response to hydrogen peroxide / protein polyubiquitination / Chaperone Mediated Autophagy / Aggrephagy / cellular response to heat / actin binding / perikaryon / microtubule binding / microtubule / regulation of autophagy
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 / Ureohydrolase domain superfamily / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
Protein deacetylase HDAC6
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.43 Å
AuthorsWang, L. / Kempf, G.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss National Science Foundation2014/264 Switzerland
Citation
Journal: Cell Rep / Year: 2022
Title: Disrupting the HDAC6-ubiquitin interaction impairs infection by influenza and Zika virus and cellular stress pathways.
Authors: Wang, L. / Moreira, E.A. / Kempf, G. / Miyake, Y. / Oliveira Esteves, B.I. / Fahmi, A. / Schaefer, J.V. / Dreier, B. / Yamauchi, Y. / Alves, M.P. / Pluckthun, A. / Matthias, P.
#1: Journal: Acta Crystallogr D Biol Crystallogr / Year: 2012
Title: Towards automated crystallographic structure refinement with phenix.refine.
Authors: Afonine, P.V. / Grosse-Kunstleve, R.W. / Echols, N. / Headd, J.J. / Moriarty, N.W. / Mustyakimov, M. / Terwilliger, T.C. / Urzhumtsev, A. / Zwart, P.H. / Adams, P.D.
History
DepositionMay 25, 2022Deposition site: PDBE / Processing site: PDBE
SupersessionJun 1, 2022ID: 7ATT
Revision 1.0Jun 1, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Mar 27, 2024Group: Database references / Category: citation
Item: _citation.page_last / _citation.pdbx_database_id_PubMed
Revision 1.3Oct 9, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone deacetylase 6
B: Designed Ankyrin repeat protein F10
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,8348
Polymers29,4522
Non-polymers3826
Water18010
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2440 Å2
ΔGint2 kcal/mol
Surface area12390 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.391, 81.391, 103.644
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221
Space group name HallP322"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+2/3
#3: -x+y,-x,z+1/3
#4: x-y,-y,-z+1/3
#5: -x,-x+y,-z+2/3
#6: y,x,-z
Components on special symmetry positions
IDModelComponents
11B-306-

HOH

-
Components

#1: Protein Histone deacetylase 6 / HD6 / Tubulin-lysine deacetylase HDAC6


Mass: 12279.010 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HDAC6, KIAA0901, JM21 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9UBN7, histone deacetylase, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides
#2: Protein Designed Ankyrin repeat protein F10


Mass: 17172.498 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli BL21(DE3) (bacteria)
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 10 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.35 Å3/Da / Density % sol: 63.29 %
Crystal growTemperature: 293 K / Method: vapor diffusion
Details: 3.6 M sodium formate, Bis-Tris 0.1M pH=6.7, 10% w/v Glycerol, 30% w/v 1,8-Diaminooctane(additive).

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: May 11, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.43→58.29 Å / Num. obs: 11398 / % possible obs: 94.4 % / Redundancy: 10.5 % / Biso Wilson estimate: 64.61 Å2 / CC1/2: 0.999 / Net I/σ(I): 19
Reflection shellResolution: 2.431→2.632 Å / Num. unique obs: 572 / CC1/2: 0.589

-
Processing

Software
NameVersionClassification
PHENIX1.19.1refinement
autoPROCdata reduction
STARANISOdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3gv4

3gv4


Resolution: 2.43→58.29 Å / SU ML: 0.2433 / Cross valid method: FREE R-VALUE / σ(F): 1.92 / Phase error: 34.0046
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2498 1071 5.06 %
Rwork0.2166 20108 -
obs0.2184 11396 73.33 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 78.11 Å2
Refinement stepCycle: LAST / Resolution: 2.43→58.29 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2029 0 15 10 2054
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00342085
X-RAY DIFFRACTIONf_angle_d0.5892835
X-RAY DIFFRACTIONf_chiral_restr0.0426318
X-RAY DIFFRACTIONf_plane_restr0.0035373
X-RAY DIFFRACTIONf_dihedral_angle_d9.4652739
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.43-2.540.342100.4158371X-RAY DIFFRACTION10.6
2.54-2.680.4514480.3678986X-RAY DIFFRACTION29.36
2.68-2.840.3751940.34491822X-RAY DIFFRACTION52.44
2.84-3.060.41111820.31013237X-RAY DIFFRACTION94.03
3.06-3.370.29591590.30683447X-RAY DIFFRACTION100
3.37-3.860.26192020.22823400X-RAY DIFFRACTION100
3.86-4.860.20311750.17743435X-RAY DIFFRACTION99.97
4.86-58.290.21582010.17013410X-RAY DIFFRACTION99.92
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.00309096137-2.04812826092.614869473833.54336803968-1.913248165854.32893451736-0.6883253955610.237212594691.07993842838-0.335348400328-0.0351714039659-0.289711637241-0.433025871770.6193633507230.3906203609870.2390220331470.506287034282-0.671695690624-0.9321960927250.868970776503-0.1583276516257.1413012668453.960219660818.5552693706
22.373608485210.833605692862.685383080210.3236636208220.6759860550279.523149834090.522605287877-0.4492496372940.675415170749-0.208064052623-0.501260873657-0.885982648927-0.89929819591-0.8408353645770.1579043488770.6071209404420.122319614572-0.09737622799020.4335798128530.0003613275828290.52625787311712.128467584864.863483579517.4630747758
30.5470646226010.6047438012320.07319744858391.372450056220.1089508462990.365548697271-0.211051863761-0.1421652194810.603495505605-0.512881042065-0.236725971135-2.28620437335-0.1492132409720.709428989521-0.2371327070990.5167866012390.0541584267544-0.184811499020.9162516076750.2994263295350.94410373474729.701443309462.549092552124.8877468695
40.207922434866-0.296891034533-0.1813240710630.7186335727350.02912270212910.4006252178991.308512178950.5649196086370.3046463420010.82435990691-0.810833654857-0.7113247880310.4596056151790.7833435587050.00905052018090.804070159038-0.0769005155858-0.4293844359350.6352506380130.2182800936930.92684979788425.79630906257.508500245434.1695534406
50.350118887782-0.29330677066-0.3654313784230.3601325004620.3714499198450.257168916489-0.0694080592301-0.283316795855-0.01550373050020.474639508308-0.264587872443-0.741768029361-0.368920078644-0.100245699624-0.006457518839680.491379167035-0.13653699469-0.2296834456780.5100803736190.1993291964740.59428972529519.765190854464.64883379530.9877283698
60.2941297491850.0648603858268-0.7166622640340.0142963198613-0.336915099734.665306018240.09955515797980.186748849184-0.142756929230.3006017818810.548415281656-1.179429372060.512972146036-0.642791022746-0.08195942693540.433507472590.13033389204-0.2711055169850.3629083486830.09105460818110.88350125911122.197545047253.802790812125.6268772937
70.700257000982-0.332194659977-1.692439228070.3398452011731.333498123375.59387177241-0.409319431246-0.7719655521160.314450098352-0.350157386770.6031067164930.675833716621.20668039417-0.411123741567-0.1006932635760.4615828616330.0380466447302-0.1424537472720.3271359780570.1389166601310.6030510902310.179393273261.002352882826.8891807394
80.1526873643590.127706879287-0.07484330189530.378276190077-0.2773576138250.171094620842-0.2416223757310.20916563895-0.931479361891-0.337992492050.0982486625295-0.7619253620680.627277629468-0.125655397242-0.0001072772782890.667358910470.176335599088-0.07429744835860.5133928948310.05077334741070.6723499348820.217861947155.136407335716.2891491997
90.07134828292160.006877486740210.05196362959790.07629388378610.02422982456040.029093349619-0.221498246481-0.882177255986-0.383443609471-0.226456675019-0.699062855763-0.7475166882680.1955822859310.154538822638.11828837809E-50.7985188943310.516639600194-0.02500609222420.9365501411970.3161961898191.2646874173629.665195004748.536244493617.5761664787
100.161514240092-0.06916607453960.1312111012350.26615838169-0.1471368433620.117523391489-0.6900662043130.4092163225950.5056729771530.7393826106270.135410450459-1.04543295419-0.9922151198930.924972528599-0.00125006411611.606589472990.0188240908357-0.2704143114490.856754394417-0.2079061979080.88127694102513.221545838571.573626281952.738496751
110.1152761512220.1364032721620.2409498735920.1785705547930.3578022953140.8229846112830.2438472798930.1550812899650.9454191110180.647303716061-0.9779580769770.2196556159970.357791302016-0.715442327754-0.003747881239461.680251513740.347776634523-0.04074397726250.7737797774790.03982960781641.213281881295.4020643933873.28773998255.2534141422
120.187247763463-0.06855002203550.02121600838920.684594170195-0.2303980395761.07094846201-0.4619744512940.08662332955620.3931991078770.5890013881650.257928518824-0.042962562886-0.4653841660910.277300722594-0.004102131764790.7696712559690.116935792014-0.2097412551570.3934402928250.03303783724070.5289601469779.2368815700560.643401897447.2058263435
139.051401986712.543133413270.06892808649310.6921693505850.09657137413271.32380715752-0.7784894628141.230602339920.1364905640571.267223384720.7662569361350.208792724452-0.883361257842-0.239152185481-0.1513578038710.7192670791930.2894969083420.03540333002930.5113938257380.05409596910580.5116242221619.6660472768550.920030715753.3170644299
141.137630977551.69414466365-0.5828942082334.94790154463-0.5577580187660.368000980793-0.3505177757520.3696958197190.0222655584798-1.490844414980.576432964931-0.5853298939540.226168771246-0.6450687026270.2576790825650.2326924362120.127078897178-0.3142742810930.5648453467970.2618620977360.410862216546.1264774574450.319122234937.6755890759
150.249665708666-0.4260028622510.02770269159230.8784714321520.6271273585880.533922450436-0.1776611728950.136263660316-0.01578902104460.6259624702120.228309197606-0.0484722193547-0.04816267537740.003603965496721.66076311536E-60.4907615632680.0473685733659-0.04173830871870.4877071037360.08140203258310.36662665509814.45342267744.131656424744.1439773237
160.721851945890.8080165864170.6396706556130.6730008697370.5368921873140.386382057273-0.01650671920670.108805652749-0.198567444467-0.2708316843910.1829381914680.2654157422850.3290773340420.4699163679945.04375507508E-60.5066091309690.029518241069-0.04143238739490.626536499370.09416465226280.42898267224211.615516901540.998352444335.4219242822
171.066624569651.102977191840.1484528767781.314765393980.2462744485260.2748316439860.826357769136-0.0241519661614-0.340684610599-0.0775564578513-0.4907764716620.2469652685050.4461504386980.8353161026550.03617734590380.4596069181970.1919658724390.02537259161320.5611505777350.04582206000510.4360571305921.780910247137.017584167341.1130938106
180.07689164986950.0185685777629-0.07308347425810.0154202726242-0.003370729603480.1078040136530.4416988097210.3127884788280.624283432570.257126380717-0.527156383626-0.02343501025640.89169371823-0.2513821152487.4137182076E-60.648669398149-0.04762783776270.0441103016490.576989977961-0.1125189156950.55611111467610.453362006829.18875354741.7999678483
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11(chain A and resid 1106:1112)AA1106 - 11121 - 7
22(chain A and resid 1113:1119)AA1113 - 11198 - 14
33(chain A and resid 1120:1135)AA1120 - 113515 - 30
44(chain A and resid 1136:1144)AA1136 - 114431 - 39
55(chain A and resid 1145:1173)AA1145 - 117340 - 68
66(chain A and resid 1174:1181)AA1174 - 118169 - 76
77(chain A and resid 1182:1188)AA1182 - 118877 - 83
88(chain A and resid 1189:1203)AA1189 - 120384 - 98
99(chain A and resid 1204:1212)AA1204 - 121299 - 107
1010(chain B and resid 3:21)BF3 - 211 - 19
1111(chain B and resid 22:30)BF22 - 3020 - 28
1212(chain B and resid 31:80)BF31 - 8029 - 78
1313(chain B and resid 81:94)BF81 - 9479 - 92
1414(chain B and resid 95:102)BF95 - 10293 - 100
1515(chain B and resid 103:124)BF103 - 124101 - 122
1616(chain B and resid 125:144)BF125 - 144123 - 142
1717(chain B and resid 145:154)BF145 - 154143 - 152
1818(chain B and resid 155:162)BF155 - 162153 - 160

+
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