[English] 日本語
Yorodumi
- PDB-6nr0: SIRT2(56-356) with covalent intermediate between mechanism-based ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6nr0
TitleSIRT2(56-356) with covalent intermediate between mechanism-based inhibitor Glucose-TM-1beta and 1'-SH ADP-ribose
ComponentsNAD-dependent protein deacetylase sirtuin-2
Keywordshydrolase/hydrolase inhibitor / inhibitor / intermediate / deacylase / HYDROLASE / hydrolase-hydrolase inhibitor complex
Function / homology
Function and homology information


cellular response to caloric restriction / negative regulation of oligodendrocyte progenitor proliferation / cellular lipid catabolic process / negative regulation of striated muscle tissue development / : / NAD-dependent histone H4K16 deacetylase activity / positive regulation of meiotic nuclear division / positive regulation of attachment of spindle microtubules to kinetochore / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity ...cellular response to caloric restriction / negative regulation of oligodendrocyte progenitor proliferation / cellular lipid catabolic process / negative regulation of striated muscle tissue development / : / NAD-dependent histone H4K16 deacetylase activity / positive regulation of meiotic nuclear division / positive regulation of attachment of spindle microtubules to kinetochore / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / paranodal junction / tubulin deacetylation / lateral loop / NLRP3 inflammasome complex assembly / peptidyl-lysine deacetylation / mitotic nuclear membrane reassembly / negative regulation of NLRP3 inflammasome complex assembly / 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 / myelination in peripheral nervous system / rDNA heterochromatin formation / protein acetyllysine N-acetyltransferase / chromatin silencing complex / regulation of phosphorylation / Initiation of Nuclear Envelope (NE) Reformation / protein deacetylation / NAD-dependent histone deacetylase activity / juxtaparanode region of axon / positive regulation of oocyte maturation / protein lysine deacetylase activity / meiotic spindle / response to redox state / regulation of myelination / histone deacetylase activity / histone acetyltransferase binding / positive regulation of execution phase of apoptosis / negative regulation of fat cell differentiation / negative regulation of peptidyl-threonine phosphorylation / glial cell projection / positive regulation of cell division / NAD+ ADP-ribosyltransferase activity / NAD+ binding / subtelomeric heterochromatin formation / negative regulation of reactive oxygen species metabolic process / positive regulation of DNA binding / heterochromatin / heterochromatin formation / epigenetic regulation of gene expression / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / cellular response to epinephrine stimulus / substantia nigra development / centriole / negative regulation of autophagy / meiotic cell cycle / ubiquitin binding / negative regulation of protein catabolic process / mitotic spindle / autophagy / histone deacetylase binding / spindle / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / myelin sheath / chromosome / cellular response to oxidative stress / midbody / growth cone / cellular response to hypoxia / perikaryon / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA-binding transcription factor binding / 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 / SIR2/SIRT2 'Small Domain' / SIR2/SIRT2 'Small Domain' / Sirtuin, catalytic core small domain superfamily / Sirtuin family / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / TPP-binding domain / DHS-like NAD/FAD-binding domain superfamily ...Sirtuin, class I / SIR2/SIRT2 'Small Domain' / SIR2/SIRT2 'Small Domain' / Sirtuin, catalytic core small domain superfamily / Sirtuin family / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / TPP-binding domain / DHS-like NAD/FAD-binding domain superfamily / Rossmann fold / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-KXG / Chem-KXJ / NAD-dependent protein deacetylase sirtuin-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.45 Å
AuthorsPrice, I.R. / Hong, J.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)1R01DK107868 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01 GM086703-07 United States
CitationJournal: Acs Chem.Biol. / Year: 2019
Title: A Glycoconjugated SIRT2 Inhibitor with Aqueous Solubility Allows Structure-Based Design of SIRT2 Inhibitors.
Authors: Hong, J.Y. / Price, I.R. / Bai, J.J. / Lin, H.
History
DepositionJan 22, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 22, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 27, 2021Group: Database references / Derived calculations
Category: citation / citation_author ...citation / citation_author / database_2 / struct_conn / struct_conn_type
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _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_conn_type.id
Revision 1.2Oct 11, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id ..._struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NAD-dependent protein deacetylase sirtuin-2
B: NAD-dependent protein deacetylase sirtuin-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)75,38118
Polymers72,3192
Non-polymers3,06216
Water2,414134
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: mass spectrometry
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
A: NAD-dependent protein deacetylase sirtuin-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,5988
Polymers36,1601
Non-polymers1,4397
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)82.310, 76.840, 114.461
Angle α, β, γ (deg.)90.000, 95.874, 90.000
Int Tables number5
Space group name H-MI121
Space group name HallC2y(x,y,-x+z)
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-ID
11
21

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11ARGARGGLNGLN(chain 'A' and (resid 57 through 180 or resid 182...AA57 - 18020 - 143
12ASPASPALAALA(chain 'A' and (resid 57 through 180 or resid 182...AA182 - 290145 - 253
13GLYGLYLYSLYS(chain 'A' and (resid 57 through 180 or resid 182...AA304 - 339267 - 302
14LEULEUGLNGLN(chain 'A' and (resid 57 through 180 or resid 182...AA341 - 355304 - 318
15KXGKXGNANA(chain 'A' and (resid 57 through 180 or resid 182...AE - F403 - 404
26ARGARGGLNGLN(chain 'B' and (resid 57 through 180 or resid 182...BB57 - 18020 - 143
27ASPASPALAALA(chain 'B' and (resid 57 through 180 or resid 182...BB182 - 290145 - 253
28GLYGLYLYSLYS(chain 'B' and (resid 57 through 180 or resid 182...BB304 - 339267 - 302
29LEULEUGLNGLN(chain 'B' and (resid 57 through 180 or resid 182...BB341 - 355304 - 318
210KXGKXGNANA(chain 'B' and (resid 57 through 180 or resid 182...BL - M403 - 404

-
Components

-
Protein , 1 types, 2 molecules AB

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


Mass: 36159.715 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SIRT2, SIR2L, SIR2L2 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3)
References: UniProt: Q8IXJ6, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides

-
Non-polymers , 7 types, 150 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-KXJ / N~2~-[3-(2-hydroxyethoxy)propanoyl]-N-phenyl-N~6~-tetradecanethioyl-L-lysinamide


Mass: 563.835 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C31H53N3O4S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-KXG / [[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-sulfanyl-oxolan-2-yl]methyl hydrogen phosphate


Mass: 575.381 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C15H23N5O13P2S / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical
ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Formula: Na
#6: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#7: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H8O3
#8: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 134 / 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: 2.49 Å3/Da / Density % sol: 55.04 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5
Details: Mixed solution of 0.44 mM protein (in buffer of 20 mM Tris/HCl pH 7.5, 160 mM NaCl) 2.5 mM NAD+, 2.5 mM Glucose-TM-1beta with an equal volume of well solution of 2 M (NH4)2SO4, 80 mM Na Acetate/HCl pH 5.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9765 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 10, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9765 Å / Relative weight: 1
ReflectionResolution: 2.45→63.693 Å / Num. obs: 25380 / % possible obs: 91.83 % / Redundancy: 2 % / Biso Wilson estimate: 41.82 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.03585 / Rrim(I) all: 0.0507 / Net I/σ(I): 13.33
Reflection shellResolution: 2.45→2.538 Å / Redundancy: 2 % / Rmerge(I) obs: 0.3884 / Mean I/σ(I) obs: 2.06 / Num. unique obs: 2474 / CC1/2: 0.722 / Rrim(I) all: 0.5493 / % possible all: 82.5

-
Processing

Software
NameVersionClassification
PHENIX1.13_2998refinement
iMOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
Cootmodel building
MolProbitymodel building
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4X3O

4x3o


Resolution: 2.45→63.69 Å / SU ML: 0.3557 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 29.1653 / Stereochemistry target values: GeoStd + Monomer Library
RfactorNum. reflection% reflectionSelection details
Rfree0.2562 1889 7.84 %RANDOM SELECTION
Rwork0.2202 22216 --
obs0.223 24105 91.83 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 51.87 Å2
Refinement stepCycle: LAST / Resolution: 2.45→63.69 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4615 0 181 134 4930
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01124934
X-RAY DIFFRACTIONf_angle_d1.33966659
X-RAY DIFFRACTIONf_chiral_restr0.2783712
X-RAY DIFFRACTIONf_plane_restr0.0074841
X-RAY DIFFRACTIONf_dihedral_angle_d25.06071881
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.45-2.520.35721250.30151524X-RAY DIFFRACTION82.95
2.52-2.590.39671230.29011524X-RAY DIFFRACTION82.76
2.59-2.670.3251280.2681593X-RAY DIFFRACTION84.49
2.67-2.770.34881380.25371651X-RAY DIFFRACTION89.36
2.77-2.880.28951450.24931645X-RAY DIFFRACTION89.59
2.88-3.010.28371540.25331702X-RAY DIFFRACTION92.66
3.01-3.170.30141550.25141747X-RAY DIFFRACTION94.3
3.17-3.370.30461510.24811764X-RAY DIFFRACTION94.99
3.37-3.630.27381490.22381797X-RAY DIFFRACTION95.67
3.63-3.990.21551510.20551769X-RAY DIFFRACTION96.1
3.99-4.570.19681510.17771832X-RAY DIFFRACTION96.87
4.57-5.760.21971590.18411803X-RAY DIFFRACTION97.13
5.76-63.690.22981600.21431865X-RAY DIFFRACTION96.66

+
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