KDM1A, KDM1B demethylate MeK5-histone H3

Histone demethylases (HDMs) belong to two groups with distinct catalytic mechanisms. KDM1A and KDM1B (formerly known as Lysine Specific Demethylases 1 and 2), belong to the flavin adenine dinucleotide (FAD)-dependent amino oxidase family, releasing formaldehyde. The reaction mechanism requires a protonatable lysine epsilon-amino group, not available in trimethylated lysines (Shi et al. 2004). KDM1A and subsequently KDM1B were shown to catalyse demethylation of monomethyl and dimethyl, but not trimethyl, histone H3 at lysine 5 (H3K4) in vitro (Shi et al. 2004, Ciccone et al. 2009).<br>Subsequently KDM1A was found to be much more proficient at catalysing demethylation of H3K4 when part of a multiprotein complex (Lee et al. 2005) and shown to catalyse demethylation of histone H3 at lysine 10 (H3K9) in vivo when associated with the androgen receptor (Metzger et al. 2007), suggesting that its substrate specificity is modulated by interacting proteins. KDM1A is a subunit of several complexes, including CtBP, Co-REST, NRD and BRAF35 (Lan et al. 2008). It is also able to catalyse demethylation of a number of non-histone proteins (Nicholson & Chen 2009).

组蛋白去甲基化酶（HDMs）分为两组，具有不同的催化机制。KDM1A 和 KDM1B（曾被称为赖氨酸特异性去甲基化酶1和2），属于黄素腺嘌呤二核苷酸（FAD）依赖的氨基酸氧化酶家族，释放甲醛。该反应机制需要可质子化的赖氨酸ε-氨基，这在三甲基化赖氨酸中是不可得的（Shi et al. 2004）。体外研究表明，KDM1A 和随后 KDM1B 能够催化单甲基和双甲基组蛋白H3（H3K4）的脱甲基化，但不能催化三甲基化组蛋白H3（H3K4）的脱甲基化（Shi et al. 2004，Ciccone et al. 2009）。随后发现，KDM1A 作为多蛋白复合体的一部分时，在催化H3K4的脱甲基化方面表现得更为高效（Lee et al. 2005），并且当与雄激素受体结合时，能够在体内催化组蛋白H3（H3K9）的脱甲基化（Metzger et al. 2007），这表明其底物特异性受到相互作用蛋白的调节。KDM1A 是多个复合物的亚基，包括CtBP、Co-REST、NRD 和 BRAF35（Lan et al. 2008）。它还能催化多种非组蛋白蛋白的脱甲基化（Nicholson & Chen 2009）。