Scientists from The Scripps Research Institute have uncovered new evidence that challenges the current theory about a process key to the way modern drugs are designed and how they work in the human body.
The new study was published October 10, 2010 in an advance, online edition of the journal Nature Chemical Biology.
Currently, the theory about ligands – compounds that bind to proteins and trigger a specific biological action – and how they bind to proteins runs along the lines of a one person-one vote paradigm. Ligands are considered to be the relatively static partner in the process, and easily rejected if the protein dramatically changes shape.
In contrast, working with the molecular systems that recognize the hormone estrogen, the new Scripps Research study found that as protein receptors change shape ligands can adapt to that change, binding productively to both active and inactive structures.
“To our great surprise, the ligand bound differently to the active and inactive conformations of the receptor,” said Kendall Nettles, an associate professor in the Department of Cancer Biology at Scripps Florida.
“This strongly suggests a novel mechanism for managing [cell] signaling activity. The implications of this are profound, both for our understanding of how ligands regulate protein activity, and as a novel approach in drug discovery.”
Source: Mika Ono
Scripps Research Institute