Figure 2
Structural characterization of LSD family. Overall structure of human (a) LSD1 (PDB code: 2h94
) and (b) LSD2 (PDB code: 4gu1
) in complex with cofactor FAD, respectively. FAD is shown in sticks with carbon in green. Three zinc atoms are shown as green spheres. The structural domains are indicated and the color scheme corresponds to that used in Fig. 1. (c) Close-up view of the coordination of the cofactor FAD (PDB code: 2uxx
), mimetic substrate (PDB codes: 2v1d
and 2uxn
) and FAD adduct of inhibitor (PDB code: 2xaj
) in the active sites of LSD1. FAD is shown as ball-and-stick and the hydrogen bonds contributed by FAD and LSD1 residues are displayed as dashed lines. Substrate-K4M: the catalytic substrate K4 of H3K4me1/2 mutated to methionine. Substrate-LYP: the catalytic substrate K4 analog (N6-methyl-N6-propyl-L-lysine). Inhibitor-TCA interacts with FAD, forming a covalent adduct (FAD–tranylcypromine adduct). FAD–TCA adduct is shown in sticks with carbon in cyan. |