title: Evaluation of phenylcyclopropylamine compounds by enzymatic assay of lysine-specific demethylase 2 in the presence of NPAC peptide.
abstract: Lysine-specific demethylase 2 (LSD2) demethylates mono- and dimethylated Lys-4 of histone H3 (H3K4me1 and H3K4me2). NPAC protein is known to interact with LSD2 and promote its H3K4 demethylase activity. In this study, we established a demethylation assay system that utilizes recombinant LSD2 in the presence of a synthetic NPAC peptide. Several phenylcyclopropylamine (PCPA)-based inhibitors were examined for their LSD2 inhibitory activity in the LSD2 enzymatic assay with the NPAC peptide. The assay results showed that the PCPA derivatives, including NCD41, selectively inhibited LSD1 in preference to LSD2.
authors.affiliation: Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo 169-8555, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Kakizawa
authors.affiliation: Graduate School of Bio-Science, Nagahama Institute of Bio-Science Technology, 1226 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Graduate School of Bio-Science, Nagahama Institute of Bio-Science Technology, 1226 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Graduate School of Bio-Science, Nagahama Institute of Bio-Science Technology, 1226 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan. Electronic address: suzukit@koto.kpu-m.ac.jp.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D010455:Peptides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011437:Propylamines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010455:Peptides; D011437:Propylamines; D011994:Recombinant Proteins; D056466:Histone Demethylases; C000595993:KDM1B protein, human; C495195:KDM1A protein, human
keywords: Histone H3K4 demethylation; Inhibitor; Lysine-specific demethylases 1 and 2 (LSD1 and LSD2); NPAC peptide