Location of an ssRNA binding region on LSD1. (A) Analysis of crystal soaks of a 5′-UUAGG-3′ RNA ligand into LSD1–CoREST crystals shows clear difference electron density (|Fo|−|Fc|) (dark gray mesh contoured at 5.5 r.m.s.d). RNA–LSD1 interactions occur along β-sheet and loop regions of LSD1 (yellow box). LSD1 and CoREST as colored in Figure 1B. (B) The 2.8 Å resolution map reveals the unambiguous identity and directionality of the RNA (pink), shown in stick representation. The difference electron density (|Fo|−|Fc|) is noted (dark gray mesh contoured at 5.5 r.m.s.d) and nucleobase density was observed for UUAG nucleotides. (C) Schematic of noncovalent interactions between the ssRNA fragment and LSD1. Dotted lines indicate RNA–LSD1 residues within 3.0 Å (as summarized in Supplemental Table 2), with conserved LSD1 residues (bold) spanning the monoamine oxidase domain (cyan/blue). (D) A close-up view of the difference density (|Fo|−|Fc|) shows the unambiguous assignment of purine (A, G) nucleobases.
