6HOY

Human Sirt6 in complex with ADP-ribose and the inhibitor trichostatin A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.155 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural Basis of Sirtuin 6 Inhibition by the Hydroxamate Trichostatin A: Implications for Protein Deacylase Drug Development.

You, W.Steegborn, C.

(2018) J Med Chem 61: 10922-10928

  • DOI: https://doi.org/10.1021/acs.jmedchem.8b01455

  • PubMed Abstract: 

    Protein lysine deacylases comprise three zinc-dependent families and the NAD + -dependent sirtuins Sirt1-7, which contribute to aging-related diseases. Few Sirt6-specific inhibitors are available. Trichostatin A, which belongs to the potent, zinc-chelating hydroxamate inhibitors of zinc-dependent deacylases, was recently found to potently and isoform-specifically inhibit Sirt6. We solved a crystal structure of a Sirt6/ADP-ribose/trichostatin A complex, which reveals nicotinamide pocket and acyl channel as binding site and provides interaction details supporting the development of improved deacylase inhibitors.


  • Organizational Affiliation

    Department of Biochemistry , University of Bayreuth , Universitätsstraße 30 , 95445 Bayreuth , Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NAD-dependent protein deacetylase sirtuin-6
A, B
302Homo sapiensMutation(s): 0 
Gene Names: SIRT6SIR2L6
EC: 3.5.1 (PDB Primary Data), 2.4.2 (UniProt), 2.3.1 (UniProt), 2.3.1.286 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q8N6T7 (Homo sapiens)
Explore Q8N6T7 
Go to UniProtKB:  Q8N6T7
PHAROS:  Q8N6T7
GTEx:  ENSG00000077463 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8N6T7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
AR6
Query on AR6

Download Ideal Coordinates CCD File 
C [auth A],
M [auth B]
[(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
C15 H23 N5 O14 P2
SRNWOUGRCWSEMX-ZQSHOCFMSA-N
TSN
Query on TSN

Download Ideal Coordinates CCD File 
K [auth A],
T [auth B]
TRICHOSTATIN A
C17 H22 N2 O3
RTKIYFITIVXBLE-QEQCGCAPSA-N
PG4
Query on PG4

Download Ideal Coordinates CCD File 
E [auth A],
O [auth B]
TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
I [auth A]
J [auth A]
Q [auth B]
G [auth A],
H [auth A],
I [auth A],
J [auth A],
Q [auth B],
R [auth B],
S [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
ZN
Query on ZN

Download Ideal Coordinates CCD File 
D [auth A],
N [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
F [auth A],
L [auth B],
P [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.155 
  • Space Group: P 63
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.291α = 90
b = 91.291β = 90
c = 143.681γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-11-14
    Type: Initial release
  • Version 1.1: 2019-04-24
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Refinement description, Structure summary