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Literature summary extracted from

  • You, W.; Steegborn, C.
    Structural basis of sirtuin 6 inhibition by the hydroxamate trichostatin A implications for protein deacylase drug development (2018), J. Med. Chem., 61, 10922-10928 .
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.B41 gene SIRT6, His-tagged full-length Sirt6 (residues 1-355) in pQE80L.1 vector is expressed in Escherichia coli strain M15[pREP4] and His-tagged Sirt6(13-308) in vector pET151-D-TOPO in Escherichia coli strain Rosetta2 (DE3) pLysS Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.3.1.B41 Sirt6/ADP-ribose/trichostatin A complex, hanging drop vapor diffusion method, 10 mg/ml purified recombinant protein Sirt6 and 10 mM ADP-ribose in 50 mM Na-phosphate buffer, pH 7.5, 0.6 mM DTT, and 5% DMSO are mixed with an equal volume of reservoir solution containing 1.6 M (NH4)2SO4, 10% PEG 400, and Bis-Tris buffer, pH 5.7, at 20°C, X-ray diffraction structure determination and analysis at 1.70 A resolution, molecular replacement using a Sirt6/ADP-ribose structure (PDB ID 3K35) as search model, modeling Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.B41 trichostatin A TSA, a potent, zinc-chelating hydroxamate inhibitors of zinc-dependent deacylases, which potently and isoform-specifically inhibits Sirt6. Sirtuin 6 inhibition mechanism, structural basis and interaction analysis, detailed overview. The binding site are nicotinamide pocket and acyl channel, binding kinetics Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.B41 NAD+ + [protein]-N6-palmitoyl-L-lysine Homo sapiens
-
 nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.B41 Homo sapiens Q8N6T7
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.B41 recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography, tag cleavage by TEV protease, reverse affinity chromatography, action exchange chromatography, and gel filtration Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.B41 NAD+ + [protein]-N6-palmitoyl-L-lysine
-
 Homo sapiens nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.B41 SIRT6
-
 Homo sapiens
2.3.1.B41 sirtuin-6
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.B41 25
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.B41 7.5
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.1.B41 NAD+
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.3.1.B41 0.45
-
 trichostatin A pH 7.5, 25°C Homo sapiens