[English] 日本語
Yorodumi
- PDB-8ak8: Human Sirt6 in complex with ADP-ribose and fragment 4-hydroxybenzamide -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ak8
TitleHuman Sirt6 in complex with ADP-ribose and fragment 4-hydroxybenzamide
ComponentsNAD-dependent protein deacetylase sirtuin-6
KeywordsHYDROLASE / Deacylase / Fragment
Function / homology
Function and homology information


histone H3K56 deacetylase activity, NAD-dependent / histone H3K18 deacetylase activity, NAD-dependent / ketone biosynthetic process / histone H3K9 deacetylase activity, hydrolytic mechanism / histone H3K9 deacetylase activity, NAD-dependent / protein delipidation / NAD+-protein-lysine ADP-ribosyltransferase activity / regulation of lipid catabolic process / chromosome, subtelomeric region / positive regulation of protein localization to chromatin ...histone H3K56 deacetylase activity, NAD-dependent / histone H3K18 deacetylase activity, NAD-dependent / ketone biosynthetic process / histone H3K9 deacetylase activity, hydrolytic mechanism / histone H3K9 deacetylase activity, NAD-dependent / protein delipidation / NAD+-protein-lysine ADP-ribosyltransferase activity / regulation of lipid catabolic process / chromosome, subtelomeric region / positive regulation of protein localization to chromatin / NAD+-protein-arginine ADP-ribosyltransferase activity / DNA damage sensor activity / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / positive regulation of stem cell differentiation / negative regulation of D-glucose import / positive regulation of chondrocyte proliferation / transposable element silencing / NAD-dependent protein lysine deacetylase activity / cardiac muscle cell differentiation / protein acetyllysine N-acetyltransferase / pericentric heterochromatin formation / protein deacetylation / histone deacetylase activity, NAD-dependent / protein localization to site of double-strand break / positive regulation of blood vessel branching / negative regulation of glycolytic process / TORC2 complex binding / negative regulation of protein localization to chromatin / positive regulation of vascular endothelial cell proliferation / histone deacetylase regulator activity / negative regulation of protein import into nucleus / regulation of double-strand break repair via homologous recombination / regulation of protein secretion / positive regulation of double-strand break repair / DNA repair-dependent chromatin remodeling / positive regulation of stem cell proliferation / lncRNA binding / negative regulation of gene expression, epigenetic / NAD+-protein mono-ADP-ribosyltransferase activity / positive regulation of stem cell population maintenance / positive regulation of telomere maintenance / regulation of lipid metabolic process / site of DNA damage / negative regulation of cellular senescence / negative regulation of transcription elongation by RNA polymerase II / Transferases; Glycosyltransferases; Pentosyltransferases / NAD+ poly-ADP-ribosyltransferase activity / NAD+ binding / negative regulation of gluconeogenesis / positive regulation of fat cell differentiation / subtelomeric heterochromatin formation / pericentric heterochromatin / response to UV / regulation of protein localization to plasma membrane / nucleosome binding / enzyme regulator activity / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / nucleotidyltransferase activity / positive regulation of protein export from nucleus / determination of adult lifespan / circadian regulation of gene expression / base-excision repair / regulation of circadian rhythm / positive regulation of insulin secretion / protein destabilization / chromatin DNA binding / Pre-NOTCH Transcription and Translation / positive regulation of fibroblast proliferation / protein import into nucleus / transcription corepressor activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / glucose homeostasis / double-strand break repair / site of double-strand break / positive regulation of cold-induced thermogenesis / Processing of DNA double-strand break ends / damaged DNA binding / chromatin remodeling / negative regulation of cell population proliferation / intracellular membrane-bounded organelle / chromatin binding / chromatin / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / DNA binding / zinc ion binding / nucleoplasm / nucleus
Similarity search - Function
Sirtuin family / : / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / DHS-like NAD/FAD-binding domain superfamily
Similarity search - Domain/homology
Chem-AR6 / 4-HYDROXYBENZAMIDE / DI(HYDROXYETHYL)ETHER / NAD-dependent protein deacylase sirtuin-6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.73 Å
AuthorsYou, W. / Steegborn, C.
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research Foundation (DFG) Germany
CitationJournal: To Be Published
Title: Development of novel Sirtuin 6 inhibitors and activators based on a protein crystallography-based fragment screen
Authors: You, W. / Steegborn, C.
History
DepositionJul 29, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 16, 2023Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NAD-dependent protein deacetylase sirtuin-6
B: NAD-dependent protein deacetylase sirtuin-6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,66626
Polymers67,2632
Non-polymers3,40324
Water3,585199
1
A: NAD-dependent protein deacetylase sirtuin-6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,34313
Polymers33,6321
Non-polymers1,71212
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: NAD-dependent protein deacetylase sirtuin-6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,32313
Polymers33,6321
Non-polymers1,69112
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)91.074, 91.074, 143.197
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number173
Space group name H-MP63
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:

Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: LYS / Beg label comp-ID: LYS / End auth comp-ID: LEU / End label comp-ID: LEU / Refine code: 1 / Auth seq-ID: 15 - 297 / Label seq-ID: 9 - 291

Dom-IDAuth asym-IDLabel asym-ID
1AA
2BB

NCS oper:
IDCodeMatrixVector
1given(1), (1), (1)
2given(0.34569, -0.938326, 0.006564), (-0.938287, -0.345739, -0.009035), (0.010747, -0.003036, -0.999938)-0.20059, 0.39995, 61.195999

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein NAD-dependent protein deacetylase sirtuin-6 / Regulatory protein SIR2 homolog 6 / SIR2-like protein 6


Mass: 33631.594 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SIRT6, SIR2L6 / Plasmid: pET151-D-TOPO / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta2 (DE3) pLysS
References: UniProt: Q8N6T7, protein acetyllysine N-acetyltransferase

-
Non-polymers , 8 types, 223 molecules

#2: Chemical ChemComp-AR6 / [(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE / Adenosine-5-Diphosphoribose


Mass: 559.316 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C15H23N5O14P2
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C4H10O3
#5: Chemical ChemComp-P6G / HEXAETHYLENE GLYCOL / POLYETHYLENE GLYCOL PEG400


Mass: 282.331 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C12H26O7 / Comment: precipitant*YM
#6: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: SO4
#7: Chemical ChemComp-HBD / 4-HYDROXYBENZAMIDE


Mass: 137.136 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C7H7NO2 / Feature type: SUBJECT OF INVESTIGATION
#8: Chemical
ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Cl
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 199 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.6 Å3/Da / Density % sol: 52.68 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.7
Details: 1.6 M (NH4)2SO4, 10% PEG 400, and Bis-Tris buffer pH 5.7
PH range: 5.7-6.2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.2 / Wavelength: 0.9184 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 5, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9184 Å / Relative weight: 1
Reflection twin
Crystal-IDIDOperatorDomain-IDFraction
11H, K, L10.668
11-K, -H, -L20.332
ReflectionResolution: 1.73→45.54 Å / Num. obs: 69954 / % possible obs: 99.9 % / Redundancy: 11.5 % / Biso Wilson estimate: 37.049 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.12 / Net I/σ(I): 13.11
Reflection shellResolution: 1.73→1.83 Å / Redundancy: 10.9 % / Mean I/σ(I) obs: 0.97 / Num. unique obs: 11245 / CC1/2: 0.4 / Rrim(I) all: 2.61 / % possible all: 99.6

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
XSCALEdata scaling
PHASERphasing
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5MF6

5mf6


Resolution: 1.73→45.54 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.958 / SU B: 1.438 / SU ML: 0.049 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.019 / ESU R Free: 0.019 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1929 2144 3.1 %RANDOM
Rwork0.1615 ---
obs0.1625 67809 99.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 97.5 Å2 / Biso mean: 37.573 Å2 / Biso min: 19.75 Å2
Baniso -1Baniso -2Baniso -3
1--13.59 Å2-0 Å2-0 Å2
2---13.59 Å2-0 Å2
3---27.18 Å2
Refinement stepCycle: final / Resolution: 1.73→45.54 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4360 0 200 199 4759
Biso mean--52.27 36.21 -
Num. residues----559
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0134642
X-RAY DIFFRACTIONr_bond_other_d0.0020.0174418
X-RAY DIFFRACTIONr_angle_refined_deg1.5521.6556294
X-RAY DIFFRACTIONr_angle_other_deg1.3191.5810191
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.5375555
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.43219.876242
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.45415764
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.7841549
X-RAY DIFFRACTIONr_chiral_restr0.0790.2590
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.025019
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021021
Refine LS restraints NCSNumber: 2145 / Type: TIGHT THERMAL / Rms dev position: 3.95 Å / Weight position: 0.5
LS refinement shellResolution: 1.73→1.775 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.364 168 -
Rwork0.319 4928 -
all-5096 -
obs--99.12 %

+
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