Figure 3

Deletion of PLD motif in TDO-2 is predicted to destabilise the interaction with haem which is essential for enzymatic activity.

(a) Part of a multiple sequence alignment of TDO of different organisms and C. elegans TDO-2; yellow = tryptophan binding site, red = haem binding site, orange = binding site for haem and tryptophan, blue = residues missing in mutant tdo-2 (ΔPLD). (b) X-ray structure of the human TDO tetramer (PDB identifier 4PW8, separate monomers in light red, blue, grey and orange), in which a haem group has been added to the model according to the 3D structure of TDO from X. campestris (green, PDB identifier NW7). Positioned nearby the haem, also in green, is the loop of residues MSPLDF which includes the PLD residues missing in the tdo-2 (ΔPLD) mutant. Amino acids on the C-terminal side of this loop are indicated in red. (c) Enlarged image of the X-ray structure of X. campestris TDO which contains haem (green) and the substrate L-Trp (orange, PDB identifier 1NW8)¹⁹. The PSE motif (yellow) is equivalent to the PLD motif in C. elegans. Through Glu 112, the motif interacts with monomer D of the tetramer, whereas through Tyr 113 and Arg 117, it forms part of the TDO active site. (d) Left: Enlarged image of MSPLDF loop in wild type C. elegans TDO-2. Right: Enlarged image of MSPLDF loop in C. elegans tdo-2 (ΔPLD) mutant. (e) Left: Enlarged image of MTALDF loop in wild type human TDO. Right: Enlarged image of MTALDF loop in human tdo (ΔALD) mutant.