Fig. 2

Ret gene analysis (a and b) and molecular models of the ATP binding site in the RET tyrosine kinase domain as well as a S811F mutant (c and d). In exon 14, heterozygous substitution mutation from TCC to TTC, changing serine to phenylalanine, was detected (p.S811F) (a, indicated by arrow), while the nucleotide at 1476 position was G (b, indicated by arrow). A molecular model of the ATP-binding site according to X-ray crystallography of the RET tyrosine kinase domain-AMP complex (Protein Data Bank; 2IVT) is shown in (c) 3-dimentionally. AMP and Ser811 respectively are represented by green and light blue spheres with some residues surrounding AMP were described by white rods in this molecular cartoon. Oxygen and nitrogen atoms are colored red and blue, respectively. An S811F mutant model was constructed based on the structure above, also is shown (d). Phe811 is depicted in yellow. Molecular modeling operations including display residue substitution, and structural optimization were performed using MOE 2014.09 software (Chemical Computing Group., Montreal, Canada)