A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors
Figure 5
Representation of the three-dimensional structures of insulin, IGF-1, and IGF-2, and of the two binding surfaces on the ligands. Ribbon representations of the three-dimensional structures of the three ligands are shown with the insulin B chain and equivalent B domains of IGF-1 and IGF-2 coloured in red, the C domains of IGF-1 and IGF-2 in pink, the insulin A chain and A domains of IGF-1 and IGF-2 in blue, and the D domains of IGF-1 and IGF-2 in green (a). The three insulin α helices, one in the B chain and two in the A chain, are visible as are the equivalent structures in IGF-1 and IGF-2. The positions and orientations of the side chains of the residues implicated in interaction of the ligands with the receptors are shown on the backbone of the molecule structures which are coloured in grey (b). The side chains are shown in ball-and-stick view. The side chains of the residues located on binding Surface 1 are coloured in pink and those located on binding Surface 2 are coloured in blue. Residues ValB12, TyrB16, GlyB23, PheB24, PheB25, TyrB26, GlyA1, IleA2, ValA3, GlnA5, TyrA19, and AsnA21 of insulin are involved in Surface 1 and HisB10, GluB13, LeuB17, SerA12, LeuA13, and GluA17 in Surface 2. For IGF-1, residues Phe23, Tyr24, Tyr31, Arg36, Arg37, Val44, Tyr60, and Ala62 form Surface 1 and residues Glu9, Asp12, Phe16, Leu54, and Glu58 are thought to contribute to Surface 2. In IGF-2, residues Val14, Phe28, and Val43 are included in Surface 1 and residues Glu12, Phe19, Leu53, and Glu57 in Surface 2.
