Acetylcholinesterase-Interacting Toxins

Use of a structural scaffold to introduce a new activity, or to change a protein's specificity, remains an exciting, but difficult, exercise in protein engineering. Particular attention has been focused on protein loops since they form continuous solvent-exposed surfaces and are frequently involved in molecular recognition and biological functions.

Three-fingered snake toxins belong to a large family of 60-70 residue proteins which share a common fold but bind to a wide range of different targets. FAS-II and a-neurotoxin are particularly good examples, since they have very similar structures, but completely different targets. Working with the Menez laboratory (CEA, Saclay, France), we are comparing the 3D structure of the complex of a chimera of these two toxins with AChE, in order to understand the structure/function relationships between the chimeras and their parent toxins in target recognition.