Fig. 5.

a Molecular model of the catechol-O-methyltransferase domain of LRTOMT2, residues 79–290. The affected residues are depicted in blue. The predicted ligands are coloured yellow, and the tyrosine residue (Tyr111) that lines the hydrophobic groove of the ligand binding site is shown in cyan. The boxed region containing residues affected by mis-sense mutations of LRTOMT2 is enlarged in panels b–d. The helices 1 (H1) and 2 (H2) are shown with wild-type residues Arg81, Trp105 and Glu110 depicted in blue and mutated residues in green. Hydrogen bonds are represented by yellow dotted lines. b The Arg81 and Glu110 residues form a salt bridge between helix 1 and the loop following helix 2. The Gln81 residue cannot form this salt bridge as it is not positively charged. Also, the formation of hydrogen bonds is impaired because of the smaller size of glutamine as compared with arginine. c The Trp105 residue is predicted to make hydrophobic interactions as a result of its large side-chain. Most of these interactions would be lost by the W105R substitution. d Substitution E110K is predicted to lead to the loss of hydrogen bonds and a salt bridge. There would likely be repulsion between the side-chains Lys110 and Arg81 as both are positively charged