› 4bvb

X-ray diffraction
2Å resolution

CRYSTAL STRUCTURE OF HUMAN SIRT3 IN COMPLEX WITH THE INHIBITOR EX-527 AND ADP-RIBOSE

Released:
DOI: 10.2210/pdb4bvb/pdb
PDB entry 4bvb coloured by chain, front view.
PDB entry 4bvb coloured by chain, side view.
PDB entry 4bvb coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism.
Gertz M, Fischer F, Nguyen GT, Lakshminarasimhan M, Schutkowski M, Weyand M, Steegborn C
Proc Natl Acad Sci U S A 110 E2772-81 (2013)
PMID: 23840057

Function and Biology Details

Reaction catalysed: 
(1a) [protein]-N(6)-acetyl-L-lysine + NAD(+) = [protein]-N(6)-(1,1-(5-adenosylyl-alpha-D-ribose-1,2-di-O-yl)ethyl)-L-lysine + nicotinamide
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-192599 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
NAD-dependent protein deacetylase sirtuin-3, mitochondrial Chain: A
Molecule details ›
Chain: A
Length: 284 amino acids
Theoretical weight: 31.48 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q9NTG7 (Residues: 116-399; Coverage: 71%)
Gene names: SIR2L3, SIRT3
Sequence domains: Sir2 family
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand OCZ 1 x OCZ
Ligand AR6 1 x AR6
Ligand ZN 1 x ZN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: BESSY BEAMLINE 14.1
Spacegroup: P212121
Unit cell:
a: 61.5Å b: 64.15Å c: 67.83Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.173 0.17 0.232
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

40 review citations

Small molecule SIRT1 activators for the treatment of aging and age-related diseases.
Hubbard et al. (2014)
39 more

6 mentions without citation

Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism.
Gertz et al. (2013)
5 more