A Novel, Homozygous c.1502T>G (p.Val501Gly) Mutation in the Thyroid peroxidase Gene in Malaysian Sisters with Congenital Hypothyroidism and Multinodular Goiter
Figure 5
Computer generated models of the wild type and mutant TPO. (a) Residues Pro-515 to Leu-519 and Pro-499 to Arg-503 are displayed in sticks for wild type and p.Val501Gly mutant TPO proteins. H-bonds are shown as green dashed lines. For the mutant protein, H-bond Gly501: HN -:Leu517: O is indicated by an arrow. (b) Ribbon presentation of wild type and p.Val501Gly mutant TPO proteins. The residues Val-501, Gly-501, and Leu-517 are shown as sticks. The H-bond between the backbone oxygen of Leu-517 and amide hydrogen of Gly-501 in the mutant contributed to the formation of a beta sheet that comprised two beta strands from Leu-500 to Arg-502 and Gly-516 to Trp-518. (Red areas represent alpha helix, cyan shows the beta-pleated sheet areas, gray areas represent coils in the protein, and green areas represent the turn.) (c) Connoly surface representation of the internal surface of TPO proteins and the binding site of heme (Glu-399) and iron (His-494) in wild type and p.Val501Gly mutant. Residues on the top layer are shown as ribbon to allow the visualization of the binding pocket. Significant structural alterations are indicated by arrows: (i) conformational changes in the heme/iron binding pocket and (ii) small “opening” from external surface. The Connolly surface is coloured according to electrostatic potential spectrum.
