Fig. 4: Structure of human LIAS in the presence of the octanoylated 8mer peptide (OCT-8mer) substrate.
From: Structural basis for catalysis by human lipoyl synthase
Structure of a the LIAS substrate binding site in the presence of the OCT-8mer substrate containing an octanoyllysyl moiety (Lys-OCT) and 5’-deoxyadenosine (5’-dAH) +Met; b the SAM-binding site of LIAS in the presence of the OCT-8mer and 5’-dAH+Met. A series of conserved residues coordinate 5’-dAH and Met. The oxygen and nitrogen atoms of Met are coordinated to the unique iron of the RS iron-sulfur ([Fe4S4]RS) cluster in a bidentate fashion. The amino group of Met forms H-bonds with the carboxyl group of Asp181 and the carbonyl oxygen of Ser179, while the Cγ of Met is in hydrophobic contact with Leu212. The adenine ring of 5’-dAH interacts with the aromatic rings of Phe143 and Tyr309, while its C4 and C5 are in van der Waals distance from Met279. 5’-dAH forms H-bonds between its N1 and the amide nitrogen of Met310, its N3 and the Nε of Arg350, its N6 and the carbonyl oxygens of Phe143 and Met310, and its ribose ring with both oxygens of the carboxyl group of Glu239 and the side chain nitrogen of Asn237. Cartoon representation of (c) superimposed structures of LIAS with no ligands (blue) and in the presence of the OCT-8mer and 5’-dAH+Met. LIAS color code: N-terminal domain (tan); RS domain (white); C-terminal α-helix (purple); iron–sulfur atoms of the auxiliary ([Fe4S4]AUX) and [Fe4S4]RS clusters are represented as orange and yellow balls, respectively. The green arrows indicate conformational changes between the two structures. The electrostatic surface potential of LIAS with no ligands (d), and in the presence of the OCT-8mer and 5’-dAH+Met (e). Structures in c–e are in the same orientation.
