Sticky switches

The binding interface between human growth hormone (hGH) and the hGH receptor has a well-defined hydrophobic core. In the 16 June Science , Guo et al. replace two residues from this region (a threonine from hGH and a tryptophan from the hGH receptor) with glycines to create a cavity. They then screen a library of around 200 indole-based compounds and find one that can restore the binding of the two mutated proteins (Science 2000, 288:2042-2045). The 1000-fold increase in binding affinity in the presence of the chemical constitutes a switch that may ultimately find applications in vivo.