[English] 日本語
Yorodumi
- PDB-8ccz: Crystal structure of human Sirt3 in complex with an inhibiting HI... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ccz
TitleCrystal structure of human Sirt3 in complex with an inhibiting HIV1 Tat-37-59 peptide
Components
  • NAD-dependent protein deacetylase sirtuin-3, mitochondrial
  • Protein Tat
KeywordsSIGNALING PROTEIN / Sirtuin / inhibitor / HIV / complex
Function / homology
Function and homology information


viral gene expression / trans-activation response element binding / regulatory region RNA binding / positive regulation of superoxide dismutase activity / positive regulation of catalase activity / protein serine/threonine phosphatase inhibitor activity / NAD-dependent protein lysine delactylase activity / positive regulation of ceramide biosynthetic process / positive regulation of viral transcription / symbiont-mediated perturbation of host chromatin organization ...viral gene expression / trans-activation response element binding / regulatory region RNA binding / positive regulation of superoxide dismutase activity / positive regulation of catalase activity / protein serine/threonine phosphatase inhibitor activity / NAD-dependent protein lysine delactylase activity / positive regulation of ceramide biosynthetic process / positive regulation of viral transcription / symbiont-mediated perturbation of host chromatin organization / Maturation of TCA enzymes and regulation of TCA cycle / peptidyl-lysine deacetylation / symbiont-mediated suppression of host translation initiation / NAD-dependent protein lysine deacetylase activity / host cell nucleolus / protein acetyllysine N-acetyltransferase / protein deacetylation / histone deacetylase activity, NAD-dependent / positive regulation of oxidative phosphorylation / actinin binding / Regulation of FOXO transcriptional activity by acetylation / protein lysine deacetylase activity / cellular response to stress / negative regulation of reactive oxygen species metabolic process / NAD+ binding / Mitochondrial unfolded protein response (UPRmt) / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / RNA-binding transcription regulator activity / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / cyclin binding / aerobic respiration / positive regulation of transcription elongation by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / positive regulation of insulin secretion / negative regulation of ERK1 and ERK2 cascade / sequence-specific DNA binding / host cell cytoplasm / symbiont-mediated suppression of host innate immune response / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / mitochondrial matrix / protein domain specific binding / DNA-templated transcription / enzyme binding / protein-containing complex / mitochondrion / extracellular region / zinc ion binding / nucleoplasm / metal ion binding / nucleus
Similarity search - Function
Tat domain superfamily / Immunodeficiency virus transactivating regulatory protein (Tat) / Transactivating regulatory protein (Tat) / 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
Protein Tat / NAD-dependent protein deacetylase sirtuin-3, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
Human immunodeficiency virus 1
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsAdolph, R.S. / Steegborn, C.
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research Foundation (DFG)STE1701/15 Germany
CitationJournal: Life / Year: 2023
Title: Molecular Mechanism of Sirtuin 1 Inhibition by Human Immunodeficiency Virus 1 Tat Protein.
Authors: Adolph, R.S. / Beck, E. / Schweimer, K. / Di Fonzo, A. / Weyand, M. / Rosch, P. / Wohrl, B.M. / Steegborn, C.
History
DepositionJan 28, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 10, 2023Provider: repository / Type: Initial release
Revision 1.1Feb 7, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NAD-dependent protein deacetylase sirtuin-3, mitochondrial
B: NAD-dependent protein deacetylase sirtuin-3, mitochondrial
C: Protein Tat
D: Protein Tat
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,2946
Polymers68,1634
Non-polymers1312
Water8,503472
1
A: NAD-dependent protein deacetylase sirtuin-3, mitochondrial
C: Protein Tat
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,1473
Polymers34,0812
Non-polymers651
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1600 Å2
ΔGint-3 kcal/mol
Surface area13730 Å2
MethodPISA
2
B: NAD-dependent protein deacetylase sirtuin-3, mitochondrial
D: Protein Tat
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,1473
Polymers34,0812
Non-polymers651
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1530 Å2
ΔGint-6 kcal/mol
Surface area13490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)54.545, 78.124, 76.575
Angle α, β, γ (deg.)90.000, 96.093, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

#1: Protein NAD-dependent protein deacetylase sirtuin-3, mitochondrial / hSIRT3 / Regulatory protein SIR2 homolog 3 / SIR2-like protein 3


Mass: 31340.084 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SIRT3, SIR2L3 / Production host: Escherichia coli (E. coli)
References: UniProt: Q9NTG7, protein acetyllysine N-acetyltransferase
#2: Protein/peptide Protein Tat / Transactivating regulatory protein


Mass: 2741.274 Da / Num. of mol.: 2 / Mutation: C37A / Source method: obtained synthetically / Details: C37A / Source: (synth.) Human immunodeficiency virus 1 / References: UniProt: P12506
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 472 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.38 Å3/Da / Density % sol: 48.32 % / Description: Plates
Crystal growTemperature: 293.15 K / Method: vapor diffusion, sitting drop
Details: 10 mg/ml human Sirt3-(118-399) in 20 mM Tris/HCl, pH 8.0, 150 mM NaCl, 5% (v/v) glycerol, 1 mM TCEP were incubated with 2 mM Tat-37-59 in 10% (v/v) DMSO for 60 min at 293.15 K. The complex ...Details: 10 mg/ml human Sirt3-(118-399) in 20 mM Tris/HCl, pH 8.0, 150 mM NaCl, 5% (v/v) glycerol, 1 mM TCEP were incubated with 2 mM Tat-37-59 in 10% (v/v) DMSO for 60 min at 293.15 K. The complex was crystallized using the sitting-drop vapor-diffusion method at 293.15 K with 100 mM CHES, pH 9.0, 20% (w/v) PEG 8000 as reservoir solution.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.9184 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 13, 2018
RadiationMonochromator: DCM Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9184 Å / Relative weight: 1
ReflectionResolution: 1.95→54.24 Å / Num. obs: 46174 / % possible obs: 98.83 % / Redundancy: 5.5 % / Biso Wilson estimate: 30.86 Å2 / CC1/2: 0.949 / CC star: 0.987 / Net I/σ(I): 11.97
Reflection shellResolution: 1.95→2.02 Å / Redundancy: 5.5 % / Mean I/σ(I) obs: 0.55 / Num. unique obs: 4615 / CC1/2: 0.445 / CC star: 0.785 / % possible all: 98.88

-
Processing

Software
NameVersionClassification
DIALSdata reduction
Aimlessdata scaling
PHASERphasing
Cootmodel building
PHENIX1.17.1_3660refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4BVB

4bvb


Resolution: 1.95→54.24 Å / SU ML: 0.2762 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 29.4121
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2763 2335 5.06 %
Rwork0.2269 43774 -
obs0.2293 46109 98.84 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 38.87 Å2
Refinement stepCycle: LAST / Resolution: 1.95→54.24 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4554 0 2 472 5028
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00194675
X-RAY DIFFRACTIONf_angle_d0.51136350
X-RAY DIFFRACTIONf_chiral_restr0.0415709
X-RAY DIFFRACTIONf_plane_restr0.0043830
X-RAY DIFFRACTIONf_dihedral_angle_d19.43491768
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.95-1.990.34841480.32372501X-RAY DIFFRACTION98.48
1.99-2.030.33121300.31292592X-RAY DIFFRACTION99.38
2.03-2.080.30491530.27992547X-RAY DIFFRACTION99.08
2.08-2.130.30861620.28442510X-RAY DIFFRACTION97.66
2.13-2.190.33231360.26652551X-RAY DIFFRACTION97.46
2.19-2.250.3571310.26142564X-RAY DIFFRACTION99.59
2.25-2.330.30471370.2592601X-RAY DIFFRACTION99.38
2.33-2.410.30641180.25452583X-RAY DIFFRACTION99.52
2.41-2.510.30871160.25612606X-RAY DIFFRACTION99.23
2.51-2.620.30571240.24752598X-RAY DIFFRACTION99.05
2.62-2.760.3481640.25012541X-RAY DIFFRACTION98.29
2.76-2.930.30891440.24192522X-RAY DIFFRACTION98.49
2.93-3.160.29431390.23242600X-RAY DIFFRACTION99.42
3.16-3.480.26411770.2232572X-RAY DIFFRACTION99.46
3.48-3.980.26031230.19962603X-RAY DIFFRACTION98.98
3.98-5.010.20321000.18112643X-RAY DIFFRACTION98.35
5.01-54.240.20971330.19952640X-RAY DIFFRACTION98.51

+
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