Figure 3
From: Use of cyclic peptides to induce crystallization: case study with prolyl hydroxylase domain 2
Structure based sequence alignment of 3C-ineracting residues in the PHDs and related oxygenases reveal the basis of its exquisite selectivity for the PHDs. (A) By contrast with many other macrocyclic peptide structures with a similar distorted β-sheet fold31, 3C has relatively few intramolecular interactions, but makes substantial more intermolecular interactions with cPHD2. 3C residues 8–11 from a parallel β-sheet with PHD2 β1 (aa 205–209) and 3C residues 1–4 form an anti-parallel β-sheet with PHD2 C-terminus (aa 400–404). Interestingly, binding of the 3C β-sheet to β1 of PHD2 extends the N-terminal side of double stranded β-helix (DSBH) core, which likely stabilizes its overall fold. (B) Structure based sequence alignment of 3C interacting regions (boxed black) in PHD1 (PDB: 5V1B), 2 and 3 with OGFOD1 (PDB: 4NHX), FTO (PDB: 4IE5), PAHX (PDB: 2A1X) and FIH (PDB: 1H2K) reveal that the 3C-binding residues are only conserved in PHDs. Dotted lines represent polar interactions of 3C with cPHD2.
