Fig. 1: Identification of a bi-substrate inhibitor of KMT9. | Nature Communications

Fig. 1: Identification of a bi-substrate inhibitor of KMT9.

From: Structure-guided design of a selective inhibitor of the methyltransferase KMT9 with cellular activity

Fig. 1

a Chemical structure of compound 1a with predicted binding mode. b MST assay to determine the dissociation constant (Kd) of compound 1a and SAM binding to KMT9. Data represent means ±s.d (n = 3 independent experiments). c FTSA for compound 1a binding to KMT9. ΔTm was calculated relative to vehicle (DMSO). Data represent means (n = 4). d Chemical structure of SAM. e FTSA for SAM binding to KMT9. Data represent means (n = 4). f Overall structure of the KMT9/compound 1a complex (PDB code 8CNC). KMT9α (yellow) and KMT9β (green) proteins are represented as ribbons. Arrows indicate the substrate channel (cyan) and the methionine pocket (brown) illustrated by surface view. Compound 1a is shown as sticks (magenta). g Hydrogen bonds between the amino group of compound 1a (magenta) and KMT9α (yellow) in the substrate branch. ΚΜΤ9α is shown as ribbon. Key residues and ligands are depicted as sticks. Contacts are represented by black dashed lines.

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