› 4jt8

X-ray diffraction
2.26Å resolution

Crystal Structure of human SIRT3 with ELT inhibitor 28 [4-(4-{2-[(2,2-dimethylpropanoyl)amino]ethyl}piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide[

Released:
DOI: 10.2210/pdb4jt8/pdb
PDB entry 4jt8 coloured by chain, front view.
PDB entry 4jt8 coloured by chain, side view.
PDB entry 4jt8 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of thieno[3,2-d]pyrimidine-6-carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3.
Disch JS, Evindar G, Chiu CH, Blum CA, Dai H, Jin L, Schuman E, Lind KE, Belyanskaya SL, Deng J, Coppo F, Aquilani L, Graybill TL, Cuozzo JW, Lavu S, Mao C, Vlasuk GP, Perni RB
J Med Chem 56 3666-79 (2013)
PMID: 23570514

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: 285 amino acids
Theoretical weight: 31.61 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9NTG7 (Residues: 118-399; Coverage: 71%)
Gene names: SIR2L3, SIRT3
Sequence domains: Sir2 family
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand ZN 1 x ZN
Ligand 1NR 1 x 1NR
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-D
Spacegroup: P65
Unit cell:
a: 117.28Å b: 117.28Å c: 45.59Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.204 0.202 0.241
Expression system: Escherichia coli

Quick links

Citations

27 review citations

The Role of Sirtuins in Antioxidant and Redox Signaling.
Singh et al. (2018)
26 more

5 mentions without citation

SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases.
Manjula et al. (2020)
4 more