Rational design of the S1H peptide.A, three-dimensional crystal structure of hGH bound to homodimeric hGHR. hGH (salmon) is shown as a ribbon diagram bound to the hGHR (gray); the site 1 mini-helix of hGH is colored purple. B, zoomed image of the site 1 mini-helix bound to the hGHR. Side chains of residues 38 to 47 are shown as stick representations. Structures adapted from PDB ID: 1HWG and rendered using PyMol Molecular Graphics System software (Schrödinger, LLC). C, amino acid sequence alignment of GH proteins from human, rat, mouse, cow, pig and sheep indicating conserved (yellow) and variable (green) amino acid residues. The S1H peptide sequence is shown in bold; alignment rendered using Multiple Sequence Alignment Tool (NCBI). GH, growth hormone; hGH, human growth hormone; hGHR, human growth hormone receptor.