Figure 34.

Mechanisms of lysine demethylation. (A) Active site of human LSD1 with bound FAD attached to the mechanism-based histone 3 peptide inhibitor N-methylpropargyl-K4 H3 (PDB 2UXN)²³⁰ and proposed mechanism. Note that the covalent inhibitor was further reduced using NaBH₄. (B) Active site of the JMJD2A with bound H3K9me3, nickel, and N-oxalylglycine that both mimic the actual iron and α-ketoglutarate cofactors, highlighted in green and gray, respectively (PDB 2OQ6),²³¹ and proposed mechanism. Green dashed lines represent CH···O hydrogen bonds. Abbreviations: FAD, flavin adenine dinucleotide; FADH, reduced flavin adenine dinucleotide; FA, formic acid; aKG, α-ketoglutarate; OGA, N-oxalylglycine.