› 5yqn

X-ray diffraction
1.6Å resolution

Crystal structure of Sirt2 in complex with selective inhibitor L55

Released:
DOI: 10.2210/pdb5yqn/pdb
PDB entry 5yqn coloured by chain, front view.
PDB entry 5yqn coloured by chain, side view.
PDB entry 5yqn coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
X-ray crystal structure guided discovery of new selective, substrate-mimicking sirtuin 2 inhibitors that exhibit activities against non-small cell lung cancer cells.
Yang LL, Wang HL, Zhong L, Yuan C, Liu SY, Yu ZJ, Liu S, Yan YH, Wu C, Wang Y, Wang Z, Yu Y, Chen Q, Li GB
Eur J Med Chem 155 806-823 (2018)
PMID: 29957526

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-184915 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
NAD-dependent protein deacetylase sirtuin-2 Chain: A
Molecule details ›
Chain: A
Length: 306 amino acids
Theoretical weight: 34.45 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q8IXJ6 (Residues: 56-356; Coverage: 77%)
Gene names: SIR2L, SIR2L2, SIRT2
Sequence domains: Sir2 family

Ligands and Environments

3 bound ligands:
Ligand ZN 1 x ZN
Ligand L55 1 x L55
Ligand PEG 1 x PEG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL19U1
Spacegroup: P21
Unit cell:
a: 35.864Å b: 73.51Å c: 55.573Å
α: 90° β: 95.18° γ: 90°
R-values:
R R work R free
0.175 0.174 0.204
Expression system: Escherichia coli

Quick links

Citations

8 review citations

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

1 mention without citation

Virtual Screening Combined with Enzymatic Assays to Guide the Discovery of Novel SIRT2 Inhibitors.
Scarano et al. (2023)