Patent ID: 8180580
Filing Date: 2012-05-15
Classification: C12Q,G01N

Abstract:
1. A method for identifying a compound that binds to or inhibits the histone deacetylase activity of a silent information regulator 2(Sir2) protein comprising: a) generating on a computer a three-dimensional structure of a nicotinamide inhibition and base exchange site of a Sir2 protein of SEQ ID NO:1 in complex with nicotinamide, wherein the nicotinamide inhibition and base exchange site consists of amino acid residues 44, 64, 67, 116, 117 and 184 of SEQ ID NO:1, wherein the structural coordinates of amino acid residues 44, 64, 67, 116, 117 and 184 of SEQ ID NO:1 and nicotinamide are obtained by X-ray diffraction of a crystal of a complex of a Sir2 protein consisting of the amino acid sequence of SEQ ID NO:1 and an N-terminal hexahistidine tag, adenosine diphosphate hydroxymethyl pyrrolidinediol, an acetyl-lysine 16 histone H4 peptide, and nicotinamide, wherein the crystal has space group P3 b) employing the three-dimensional structure of the nicotinamide inhibition and base exchange site to design or screen for a compound that potentially binds to said nicotinamide inhibition and base exchange site; and c) testing the compound designed or screened for in (b) by contacting the compound with the Sir2 protein of SEQ ID NO:1 and identifying compounds that bind to or inhibit the histone deacetylase activity of the Sir2 protein of SEQ ID NO:1.