[English] 日本語
Yorodumi
- PDB-4zzi: SIRT1/Activator/Inhibitor Complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4zzi
TitleSIRT1/Activator/Inhibitor Complex
ComponentsNAD-dependent protein deacetylase sirtuin-1
KeywordsHydrolase/hydrolase inhibitor / Sirtuin / Activator / Deacylase / Complex / Hydrolase-hydrolase inhibitor complex
Function / homology
Function and homology information


negative regulation of prostaglandin biosynthetic process / regulation of smooth muscle cell apoptotic process / maintenance of nucleus location / histone H3K deacetylase activity / NAD-dependent histone decrotonylase activity / negative regulation of attachment of mitotic spindle microtubules to kinetochore / negative regulation of cellular response to testosterone stimulus / protein depropionylation / NAD-dependent protein-lysine depropionylase activity / histone H3K14 deacetylase activity, NAD-dependent ...negative regulation of prostaglandin biosynthetic process / regulation of smooth muscle cell apoptotic process / maintenance of nucleus location / histone H3K deacetylase activity / NAD-dependent histone decrotonylase activity / negative regulation of attachment of mitotic spindle microtubules to kinetochore / negative regulation of cellular response to testosterone stimulus / protein depropionylation / NAD-dependent protein-lysine depropionylase activity / histone H3K14 deacetylase activity, NAD-dependent / eNoSc complex / regulation of peroxisome proliferator activated receptor signaling pathway / regulation of transcription by glucose / histone H4K12 deacetylase activity, hydrolytic mechanism / positive regulation of macrophage apoptotic process / negative regulation of triglyceride biosynthetic process / regulation of endodeoxyribonuclease activity / triglyceride mobilization / behavioral response to starvation / pyrimidine dimer repair by nucleotide-excision repair / keratin filament binding / HLH domain binding / regulation of lipid storage / Regulation of MITF-M dependent genes involved in metabolism / histone H3K9 deacetylase activity, NAD-dependent / leptin-mediated signaling pathway / negative regulation of peptidyl-lysine acetylation / positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / histone H4K16 deacetylase activity, NAD-dependent / regulation of brown fat cell differentiation / deacetylase activity / positive regulation of smooth muscle cell differentiation / bHLH transcription factor binding / response to leptin / peptidyl-lysine acetylation / intracellular triglyceride homeostasis / negative regulation of androgen receptor signaling pathway / positive regulation of adaptive immune response / regulation of centrosome duplication / negative regulation of phosphorylation / rDNA heterochromatin / ovulation from ovarian follicle / single strand break repair / regulation of bile acid biosynthetic process / NAD-dependent protein lysine deacetylase activity / negative regulation of signal transduction by p53 class mediator / rDNA heterochromatin formation / protein acetyllysine N-acetyltransferase / negative regulation of protein acetylation / histone deacetylase activity, NAD-dependent / chromatin silencing complex / protein deacetylation / positive regulation of MHC class II biosynthetic process / UV-damage excision repair / DNA methylation-dependent constitutive heterochromatin formation / protein lysine deacetylase activity / negative regulation of TOR signaling / positive regulation of cAMP-dependent protein kinase activity / negative regulation of helicase activity / mitogen-activated protein kinase binding / Regulation of FOXO transcriptional activity by acetylation / nuclear inner membrane / positive regulation of macrophage cytokine production / muscle organ development / DNA repair-dependent chromatin remodeling / positive regulation of double-strand break repair / stress-induced premature senescence / negative regulation of NF-kappaB transcription factor activity / histone deacetylase activity / DNA synthesis involved in DNA repair / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / negative regulation of fat cell differentiation / : / intracellular glucose homeostasis / negative regulation of cellular senescence / negative regulation of DNA damage response, signal transduction by p53 class mediator / positive regulation of macroautophagy / macrophage differentiation / negative regulation of cell cycle / white fat cell differentiation / regulation of glucose metabolic process / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / NAD+ binding / positive regulation of cholesterol efflux / Regulation of HSF1-mediated heat shock response / positive regulation of blood vessel endothelial cell migration / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / fatty acid homeostasis / Transcriptional and post-translational regulation of MITF-M expression and activity / heterochromatin / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / cellular response to glucose starvation / negative regulation of canonical NF-kappaB signal transduction / positive regulation of insulin receptor signaling pathway / regulation of cellular response to heat / energy homeostasis / positive regulation of gluconeogenesis / positive regulation of endothelial cell proliferation / regulation of mitotic cell cycle / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups
Similarity search - Function
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 ...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-1NS / Chem-4TQ / NAD-dependent protein deacetylase sirtuin-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7346 Å
AuthorsDai, H.
CitationJournal: Nat Commun / Year: 2015
Title: Crystallographic structure of a small molecule SIRT1 activator-enzyme complex.
Authors: Dai, H. / Case, A.W. / Riera, T.V. / Considine, T. / Lee, J.E. / Hamuro, Y. / Zhao, H. / Jiang, Y. / Sweitzer, S.M. / Pietrak, B. / Schwartz, B. / Blum, C.A. / Disch, J.S. / Caldwell, R. / ...Authors: Dai, H. / Case, A.W. / Riera, T.V. / Considine, T. / Lee, J.E. / Hamuro, Y. / Zhao, H. / Jiang, Y. / Sweitzer, S.M. / Pietrak, B. / Schwartz, B. / Blum, C.A. / Disch, J.S. / Caldwell, R. / Szczepankiewicz, B. / Oalmann, C. / Yee Ng, P. / White, B.H. / Casaubon, R. / Narayan, R. / Koppetsch, K. / Bourbonais, F. / Wu, B. / Wang, J. / Qian, D. / Jiang, F. / Mao, C. / Wang, M. / Hu, E. / Wu, J.C. / Perni, R.B. / Vlasuk, G.P. / Ellis, J.L.
History
DepositionMay 22, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 15, 2015Provider: repository / Type: Initial release
Revision 1.1Sep 23, 2015Group: Data collection
Revision 1.2Sep 27, 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_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NAD-dependent protein deacetylase sirtuin-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,0684
Polymers40,1251
Non-polymers9423
Water46826
1
A: NAD-dependent protein deacetylase sirtuin-1
hetero molecules

A: NAD-dependent protein deacetylase sirtuin-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)82,1358
Polymers80,2512
Non-polymers1,8856
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation10_664-y+1,-x+1,-z-1/61
Buried area2020 Å2
ΔGint-20 kcal/mol
Surface area31730 Å2
MethodPISA
Unit cell
Length a, b, c (Å)122.150, 122.150, 104.920
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number178
Space group name H-MP6122
Components on special symmetry positions
IDModelComponents
11A-825-

HOH

-
Components

#1: Protein NAD-dependent protein deacetylase sirtuin-1 / hSIRT1 / Regulatory protein SIR2 homolog 1 / SIR2-like protein 1 / hSIR2


Mass: 40125.262 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SIRT1, SIR2L1 / Production host: Escherichia coli (E. coli)
References: UniProt: Q96EB6, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides
#2: Chemical ChemComp-4TQ / (3S)-1,3-dimethyl-N-[3-(1,3-oxazol-5-yl)phenyl]-6-[3-(trifluoromethyl)phenyl]-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide


Mass: 493.480 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H22F3N5O2
#3: Chemical ChemComp-1NS / 4-(4-{2-[(methylsulfonyl)amino]ethyl}piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide


Mass: 383.489 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H21N5O3S2
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 26 / 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: 2.82 Å3/Da / Density % sol: 56.32 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop
Details: 0.55 M Sodium chloride, 0.1 M MES pH 6.5, and 20 % w/v PEG 4000

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.12713 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Feb 4, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.12713 Å / Relative weight: 1
ReflectionResolution: 2.73→39.983 Å / Num. obs: 12735 / % possible obs: 99.9 % / Redundancy: 17.6 % / Rmerge(I) obs: 0.053 / Net I/σ(I): 38.8
Reflection shellResolution: 2.73→2.95 Å / Redundancy: 18.2 % / Rmerge(I) obs: 0.803 / Mean I/σ(I) obs: 4 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.9_1692refinement
PHASERphasing
xia2data reduction
xia2data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3GLU and 4IG9

3glu

4ig9


Resolution: 2.7346→39.983 Å / SU ML: 0.27 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 25.81 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2346 636 5.01 %
Rwork0.1908 --
obs0.1931 12698 99.88 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.7346→39.983 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2679 0 62 26 2767
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0042814
X-RAY DIFFRACTIONf_angle_d0.8983826
X-RAY DIFFRACTIONf_dihedral_angle_d14.8951089
X-RAY DIFFRACTIONf_chiral_restr0.031417
X-RAY DIFFRACTIONf_plane_restr0.007495
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.7346-2.94570.30031230.23652344X-RAY DIFFRACTION100
2.9457-3.2420.2841250.2162367X-RAY DIFFRACTION100
3.242-3.71090.26531260.19852377X-RAY DIFFRACTION100
3.7109-4.67420.20961260.17142417X-RAY DIFFRACTION100
4.6742-39.98720.22241360.19052557X-RAY DIFFRACTION100
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)
18.87473.11911.86533.10283.048210.5411-0.155-0.7198-0.41320.71880.2378-1.0511-0.18660.4848-0.40150.87870.2202-0.17170.6228-0.04570.603911.072849.1881-19.4313
23.0485-0.40170.83522.5080.0043.2478-0.06680.15580.25360.34290.13260.4307-0.0805-0.34780.0150.5437-0.0113-0.00990.4987-0.10830.70141.357158.2399-5.5357
39.0527-2.9168-2.50786.69493.81228.4122-0.13170.6869-0.46520.19270.2032-0.84340.79940.4894-0.03920.56650.02590.13890.4412-0.02060.674612.709636.9425-3.7339
46.8198-0.5825-0.34614.08181.65735.5813-0.3298-0.1245-1.51530.7421-0.124-0.0351.1127-0.10420.37480.8648-0.03850.18840.50770.08420.69946.156833.50174.5676
53.43371.8961.23238.06463.81533.188-0.138-0.1013-2.15911.6180.17990.6742.2749-0.4015-0.011.5269-0.2740.50780.7868-0.08661.57364.824520.70442.2094
62.285-0.0691-1.64487.1453-3.16382.74630.43310.7529-2.05940.9348-0.0386-0.82532.5293-0.1825-0.27582.1089-0.25880.14880.7535-0.31131.98727.193912.1608-3.6699
75.45210.4219-1.75095.81291.91532.9907-0.1620.8865-0.68320.4137-0.26790.65870.3768-1.30010.34610.5735-0.0520.18830.9383-0.06040.6054-4.326839.8283-2.2725
88.19152.24241.96586.11231.35586.8906-0.1277-0.0190.41120.3861-0.00740.1113-0.0711-0.05110.13680.46180.06010.07390.4506-0.07830.34663.668153.65073.1571
93.45741.3706-1.47455.5221-5.27268.5197-0.4743-0.7685-0.04461.7298-0.0702-0.2713-0.136-0.26270.59951.0681-0.0274-0.00740.5791-0.1330.516410.500557.618511.1329
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 183 through 216 )
2X-RAY DIFFRACTION2chain 'A' and (resid 217 through 252 )
3X-RAY DIFFRACTION3chain 'A' and (resid 253 through 298 )
4X-RAY DIFFRACTION4chain 'A' and (resid 299 through 361 )
5X-RAY DIFFRACTION5chain 'A' and (resid 362 through 388 )
6X-RAY DIFFRACTION6chain 'A' and (resid 389 through 409 )
7X-RAY DIFFRACTION7chain 'A' and (resid 410 through 447 )
8X-RAY DIFFRACTION8chain 'A' and (resid 448 through 493 )
9X-RAY DIFFRACTION9chain 'A' and (resid 494 through 655 )

+
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