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. Author manuscript; available in PMC: 2019 Jan 7.
Published in final edited form as: J Med Chem. 2018 Mar 23;61(7):3193–3208. doi: 10.1021/acs.jmedchem.8b00261

Figure 2.

Figure 2.

Structure of ternary complex of N46-KDM5A-Mn(II) at 1.22 Å resolution (PDB code 6BGY). (A) Six metal ligands involving three protein residues, two water molecules, and the ring nitrogen atom of pyridine. The omit electron densities, contoured at 10σ and 5σ above the mean, are shown for Mn(II) (magenta mesh) and compound N46 (gray mesh), respectively. (B) The carboxylate group of pyridine-7-carboxylic acid moiety forms ionic and hydrogen bonding interactions with Lys501 and Tyr409. (C) Extensive van der Waals contacts formed between pyridine ring and 2-chlorophenyl ring of N46 and aromatic residues of KDM5A in the active site. (D) The chlorine atom of 2-chlorophenyl ring binds in a hydrophobic pocket formed by Ala411, Tyr409, and Tyr472.