GPCRs win 2012 Nobel Prize in Chemistry

What a nice surprise! Ever since Brian Kobilka's group solved the first GPCR-G protein structure I have been convinced that he and others will win the Nobel Prize. But I didn't think it would happen so soon.

In any case, amble over to my Scientific American blog for a writeup. This has to be one of the fastest discovery-to-prize transitions in recent years. It's interesting that the prize was awarded to Lefkowitz and Kobilka. I think this was done partly to recognize Lefkowitz's early pioneering work, but also because a purely structural prize would have had to recognize Raymond Stevens and Krzysztof Palczewski in my opinion. It was a shrewd move on the part of the committee to hand out a broader GPCR prize and include Lefkowitz. As for Kobilka, I think it's fair to say that among the three groups his has probably done the most detailed crystallography work.

Personally I feel very satisfied since GPCRs have been an interest of mine for a while. I have blogged about them several times and once wrote a major research proposal on them. However, as significant as the discovery is, there's still a long road ahead. There's almost a thousand GPCRs from class A-F. The present structures constitute only a handful of members of class A GPCRs (although I hear class B is coming up soon). We are far from any complete picture of GPCRs signaling and we also don't understand functional selectivity yet. This discovery has every indication of being a grand beginning than an end. 

And I have to say that the whole "But is this chemistry?!" meme is getting quite boring. Binding of a small molecule to a GPCR is as much of a molecular interaction as anything in chemistry. Plus, think about the downstream chemistry that GPCRs do, including phosphorylation of the G proteins and salt-bridge breakage in the crucial helices that modulate the signal transduction. I thought chemists were supposed to rub their hands with glee at the reduction of biology to chemistry while biologists fret and fume. But I see the opposite, biologists being quite sanguine about proteins being awarded medicine Nobels while chemists continue to complain about proteins (chemicals!) being awarded chemistry Nobels. Something's not quite right here. In addition, this year's Nobel continues the proud tradition of honoring crystallographers, a tradition that goes back to 1962 when Kendrew and Perutz won it for hemoglobin and myoglobin. The point is that chemistry has traditionally been defined as structure and function. Chemists have studied the molecular constitution of matter since the birth of the science, and biological matter is no different in principle. Why would chemists complain when structure - of any kind - is recognized by a Nobel Prize?

However there is a bright side to the arguments. As I have said before, this very bickering shows the astonishing reach and diversity of the field. If you can't even agree on a definition for your field, well, that means your field is truly everywhere.

Congratulations to Kobilka and Lefkowitz, and a toast to more GPCR research!