It may very well be that models used for the design of new drugs have to be regarded as impractical. This is the sobering though important conclusion of the work of two Leiden University scientists published in Science this week.
The editorial board of the renowned journal even decided to accelerate the publication on the crystal structure of the adenosine A2A receptor via Science Express. Together with an expert team at the Scripps Institute (La Jolla) led by crystallographer Ray Stevens, Ad IJzerman, head of the division of medicinal chemistry at the Leiden/Amsterdam Center for Drug Research, and postdoctoral fellow Rob Lane worked on the structure elucidation of this protein, which is one of caffeine's main targets in the human body, and a key player in Parkinson's disease.
Obtaining a crystal structure of a receptor bound to a drug is by far the best way to learn and appreciate how drugs actually work. "For decades scientists from all over the world have struggled to get the crystal structure of this type of G protein-coupled receptor", IJzerman explains. "These arduous attempts are easily understood when one takes into account that the whole family of these proteins are the targets for almost half of the medicines that are available in the pharmacy shop. It seemed an impossible task, since these proteins are in the cell wall, which means they are in a fatty environment, and are fatty themselves. We all know that fat does not crystallize easily."