Structural Biology Brussels - SBB
Publication date 24.01.2012
Protein structures for health
Since 2007, the "Structural Biology Brussels"’ department of the VUB is coordinating an Impulse project entitled "3D4health". Two teams from the the Université Libre de Bruxelles are the other partners of this Brussels-based consortium.
Drugs targeting G protein-coupled receptors (GPCRs) are accounted for about 25% of the worldwide pharmaceutical market in 2009. Ion-channels and transporters represent the second largest class of drug targets and it is expected that membrane proteins will continue to constitute the majority of future drug targets.
With the overall decline of new-marketed drugs in the pharmaceutical industry, one of the sector’s greatest hopes now resides in structure-based drug development. But structural knowledge of membrane proteins has so far proven extremely difficult to generate. In phase I of the 3D4Health project, the researchers demonstrated the power of Xaperones™ to generate diffracting quality crystals of the most challenging membrane proteins including GPCRs and transmembrane signaling complexes.
Xaperones™ are single domain antigen binding fragments from heavy-chain only antibodies from Camelids. By rigidifying flexible regions and obscuring aggregative surfaces, Xaperone complexes guarantee conformationally uniform samples that are key to protein structure determination by X-ray crystallography. An unanticipated but important finding was that Xaperones™ can selectively stabilize distinct conformers of conformationally rich membrane proteins. The goal of 3D4Health phase II will be to turn this technology platform into a robust pipeline for generating Xaperones™ that stabilize unique therapeutic conformations of many therapeutic targets. Jan Steyaert, the mentor of 3D4Health, anticipates that drug targets locked in their therapeutic conformations will be a much better starting point for future drug discovery.
On the occasion of the publication of two articles in Nature, the team launched the online service facility Xaperones.com, addressing 300 drug companies with activities in structural biology worldwide.
Vrije Universiteit Brussel
Department Structural Biology Brussels