[English] 日本語
Yorodumi
- PDB-8qt2: Crystal structure of human Sirt2 in complex with the super-slow s... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8qt2
TitleCrystal structure of human Sirt2 in complex with the super-slow substrate TNFn-6
Components
  • NAD-dependent protein deacetylase sirtuin-2
  • Peptide-based super-slow substrate TNFn-6
KeywordsHYDROLASE / Super-slow substrate / Sirtuin 2
Function / homology
Function and homology information


cellular response to caloric restriction / negative regulation of oligodendrocyte progenitor proliferation / : / negative regulation of striated muscle tissue development / negative regulation of satellite cell differentiation / histone H4K16 deacetylase activity, NAD-dependent / positive regulation of attachment of spindle microtubules to kinetochore / positive regulation of meiotic nuclear division / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity ...cellular response to caloric restriction / negative regulation of oligodendrocyte progenitor proliferation / : / negative regulation of striated muscle tissue development / negative regulation of satellite cell differentiation / histone H4K16 deacetylase activity, NAD-dependent / positive regulation of attachment of spindle microtubules to kinetochore / positive regulation of meiotic nuclear division / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / tubulin deacetylation / paranodal junction / lateral loop / NLRP3 inflammasome complex assembly / peptidyl-lysine deacetylation / negative regulation of NLRP3 inflammasome complex assembly / mitotic nuclear membrane reassembly / tubulin deacetylase activity / regulation of exit from mitosis / paranode region of axon / Schmidt-Lanterman incisure / NAD-dependent protein lysine deacetylase activity / positive regulation of fatty acid biosynthetic process / rDNA heterochromatin formation / protein acetyllysine N-acetyltransferase / myelination in peripheral nervous system / histone deacetylase activity, NAD-dependent / chromatin silencing complex / Initiation of Nuclear Envelope (NE) Reformation / protein deacetylation / positive regulation of oocyte maturation / regulation of phosphorylation / juxtaparanode region of axon / protein lysine deacetylase activity / meiotic spindle / response to redox state / regulation of myelination / histone deacetylase activity / histone acetyltransferase binding / positive regulation of DNA binding / negative regulation of fat cell differentiation / negative regulation of peptidyl-threonine phosphorylation / positive regulation of execution phase of apoptosis / glial cell projection / positive regulation of cell division / NAD+-protein poly-ADP-ribosyltransferase activity / NAD+ binding / negative regulation of reactive oxygen species metabolic process / subtelomeric heterochromatin formation / heterochromatin / cellular response to epinephrine stimulus / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / substantia nigra development / centriole / epigenetic regulation of gene expression / negative regulation of autophagy / ubiquitin binding / meiotic cell cycle / negative regulation of protein catabolic process / heterochromatin formation / mitotic spindle / histone deacetylase binding / autophagy / spindle / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / myelin sheath / chromosome / cellular response to oxidative stress / cellular response to hypoxia / growth cone / midbody / perikaryon / DNA-binding transcription factor binding / proteasome-mediated ubiquitin-dependent protein catabolic process / microtubule / chromosome, telomeric region / regulation of cell cycle / cell division / innate immune response / negative regulation of DNA-templated transcription / centrosome / chromatin binding / nucleolus / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / mitochondrion / zinc ion binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Sirtuin, class I / Sirtuin, catalytic core small domain superfamily / Sirtuin family / : / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / DHS-like NAD/FAD-binding domain superfamily
Similarity search - Domain/homology
(R,R)-2,3-BUTANEDIOL / : / NAD-dependent protein deacetylase sirtuin-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.65 Å
AuthorsFriedrich, F. / Kalbas, D. / Meleshin, M. / Einsle, O. / Schutkowski, M. / Jung, M.
Funding support Germany, 2items
OrganizationGrant numberCountry
German Research Foundation (DFG)SFB 992 Germany
German Research Foundation (DFG)295/18-1 Germany
CitationJournal: To Be Published
Title: New Super-Slow Substrates as novel Sirtuin-Inhibitors
Authors: Friedrich, F. / Kalbas, D. / Einsle, O. / Jung, M. / Schutkowski, M.
History
DepositionOct 12, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 23, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NAD-dependent protein deacetylase sirtuin-2
B: Peptide-based super-slow substrate TNFn-6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,1537
Polymers35,4242
Non-polymers7295
Water4,107228
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2460 Å2
ΔGint-2 kcal/mol
Surface area14270 Å2
MethodPISA
Unit cell
Length a, b, c (Å)36.041, 73.370, 55.119
Angle α, β, γ (deg.)90.00, 95.41, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein / Protein/peptide , 2 types, 2 molecules AB

#1: Protein NAD-dependent protein deacetylase sirtuin-2 / Regulatory protein SIR2 homolog 2 / SIR2-like protein 2


Mass: 34416.727 Da / Num. of mol.: 1 / Fragment: UNP residues 56-356
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SIRT2, SIR2L, SIR2L2 / Production host: Escherichia coli (E. coli)
References: UniProt: Q8IXJ6, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides
#2: Protein/peptide Peptide-based super-slow substrate TNFn-6


Mass: 1007.121 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)

-
Non-polymers , 6 types, 233 molecules

#3: Chemical ChemComp-ZN / ZINC ION


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


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-BTB / 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / BIS-TRIS BUFFER


Mass: 209.240 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H19NO5 / Comment: pH buffer*YM
#6: Chemical ChemComp-BU3 / (R,R)-2,3-BUTANEDIOL


Mass: 90.121 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O2
#7: Chemical ChemComp-WU8 / 3-dodecylsulfanyl-2,2-dimethyl-propanoic acid


Mass: 302.516 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H34O2S / Feature type: SUBJECT OF INVESTIGATION
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 228 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.03 Å3/Da / Density % sol: 39.49 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: 26.5 % (w/v) PEG 3,350 in 0.1 M Bis-Tris pH 6.5.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-3 / Wavelength: 0.9677 Å
DetectorType: DECTRIS EIGER X 4M / Detector: PIXEL / Date: Jun 22, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9677 Å / Relative weight: 1
ReflectionResolution: 1.65→54.87 Å / Num. obs: 33906 / % possible obs: 98.5 % / Redundancy: 6.1 % / CC1/2: 0.999 / Rmerge(I) obs: 0.068 / Rpim(I) all: 0.03 / Rrim(I) all: 0.074 / Χ2: 1.06 / Net I/σ(I): 14.4 / Num. measured all: 208487
Reflection shellResolution: 1.65→1.68 Å / Redundancy: 6.4 % / Rmerge(I) obs: 0.692 / Mean I/σ(I) obs: 2.5 / Num. unique obs: 1689 / CC1/2: 0.814 / Rpim(I) all: 0.297 / Rrim(I) all: 0.755 / Χ2: 1.02

-
Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
Aimlessdata scaling
autoPROCdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.65→54.87 Å / SU ML: 0.17 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 19.66 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1968 1711 5.05 %
Rwork0.1701 --
obs0.1714 33881 98.43 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.65→54.87 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2406 0 25 228 2659
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0062529
X-RAY DIFFRACTIONf_angle_d0.8053421
X-RAY DIFFRACTIONf_dihedral_angle_d12.945983
X-RAY DIFFRACTIONf_chiral_restr0.05369
X-RAY DIFFRACTIONf_plane_restr0.007439
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.65-1.70.28291310.22192724X-RAY DIFFRACTION99
1.7-1.750.24271510.20422652X-RAY DIFFRACTION99
1.75-1.820.21671580.21212678X-RAY DIFFRACTION99
1.82-1.890.22131600.19152661X-RAY DIFFRACTION99
1.89-1.970.22911270.17922679X-RAY DIFFRACTION98
1.97-2.080.21191380.17322660X-RAY DIFFRACTION98
2.08-2.210.20151520.17742680X-RAY DIFFRACTION99
2.21-2.380.21651280.172537X-RAY DIFFRACTION93
2.38-2.620.19581480.18322661X-RAY DIFFRACTION98
2.62-30.23911540.1772714X-RAY DIFFRACTION100
3-3.780.1721400.1642722X-RAY DIFFRACTION100
3.78-54.870.15651240.1452802X-RAY DIFFRACTION100
Refinement TLS params.Method: refined / Origin x: 6.9603 Å / Origin y: 17.292 Å / Origin z: 18.1045 Å
111213212223313233
T0.1039 Å2-0.0003 Å2-0.0043 Å2-0.1357 Å2-0.0087 Å2--0.1523 Å2
L0.5599 °2-0.2141 °2-0.1029 °2-0.7069 °2-0.2971 °2--1.7129 °2
S0.0134 Å °0.0373 Å °-0.0421 Å °-0.0409 Å °0.0314 Å °0.0822 Å °-0.0258 Å °-0.2777 Å °-0.0402 Å °
Refinement TLS groupSelection details: all

+
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