› 4buz

X-ray diffraction
1.9Å resolution

SIR2 COMPLEX STRUCTURE MIXTURE OF EX-527 INHIBITOR AND REACTION PRODUCTS OR OF REACTION SUBSTRATES P53 PEPTIDE AND NAD

Released:
DOI: 10.2210/pdb4buz/pdb
PDB entry 4buz coloured by chain, front view.
PDB entry 4buz coloured by chain, side view.
PDB entry 4buz coloured by chain, top view.
Source organisms:
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:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138128 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
NAD-dependent protein deacetylase Chain: A
Molecule details ›
Chain: A
Length: 246 amino acids
Theoretical weight: 27.57 KDa
Source organism: Thermotoga maritima
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q9WYW0 (Residues: 1-246; Coverage: 100%)
Gene names: TM_0490, cobB, sir2
Sequence domains: Sir2 family
Structure domains:
Cellular tumor antigen p53 Chain: P
Molecule details ›
Chain: P
Length: 8 amino acids
Theoretical weight: 1.13 KDa
Source organism: Homo sapiens
Expression system: Not provided
UniProt:
  • Canonical: P04637 (Residues: 379-386; Coverage: 2%)
Gene names: P53, TP53

Ligands and Environments

5 bound ligands:
Ligand OCZ 1 x OCZ
Ligand NAD 1 x NAD
Ligand OAD 1 x OAD
Ligand ZN 1 x ZN
Ligand EDO 1 x EDO
1 modified residue:
Ligand ALY 1 x ALY

Experiments and Validation Details

Entry percentile scores
X-ray source: BESSY BEAMLINE 14.1
Spacegroup: P212121
Unit cell:
a: 46.75Å b: 59.92Å c: 109.03Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.161 0.159 0.194
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

39 review citations

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

7 mentions without citation

Acylation of Biomolecules in Prokaryotes: a Widespread Strategy for the Control of Biological Function and Metabolic Stress.
Hentchel et al. (2015)
6 more